Advances in Colloid and Interface Science 207 (2014) 6580

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Advances in Colloid and Interface Science

journal homepage: www.elsevier.com/locate/cis

Microcapsule mechanics: From stability to function

Martin P. Neubauer, Melanie Poehlmann, Andreas Fery
University of Bayreuth, Department of Physical Chemistry II, Universittsstrae 30, 95440 Bayreuth, Germany

a r t i c l e i n f o a b s t r a c t

Available online 2 December 2013 Microcapsules are reviewed with special emphasis on the relevance of controlled mechanical properties for func-
tional aspects. At rst, assembly strategies are presented that allow control over the decisive geometrical param-
Keywords: eters, diameter and wall thickness, which both inuence the capsule's mechanical performance. As one of the
Microcapsules most powerful approaches the layer-by-layer technique is identied. Subsequently, ensemble and, in particular,
Mechanical characterization single-capsule deformation techniques are discussed. The latter generally provide more in-depth information
Shell theory
and cover the complete range of applicable forces from smaller than pN to N. In a theory chapter, we illustrate
Layer-by-layer
Drug delivery
the physics of capsule deformation. The main focus is on thin shell theory, which provides a useful approximation
for many deformation scenarios. Finally, we give an overview of applications and future perspectives where the
specic design of mechanical properties turns microcapsules into (multi-)functional devices, enriching especially
life sciences and material sciences.
2013 Elsevier B.V. All rights reserved.

Contents

1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 65
2. Microcapsules: denition and assembly strategies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 65
3. Mechanical characterization of microcapsules . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 66
4. Modeling physics of capsule deformation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 68
5. Functionality and application perspectives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 73
6. Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 76
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 76

1. Introduction of microcapsules was established for carbonless copy paper already in

Microcapsule-research is a classical example of a eld, which has
been driven and fueled by many disciplines ranging from biophysics,
via fundamental colloid- and interface research in physical chemistry
and synthesis both organic and inorganic up to applied sciences
and engineering. Microcapsules have been an object of research in
these areas for many decades. First studies date back as early as to the
1930s, when Bungenberg de Jong and co-workers investigated coacer-
vates which can be seen as the rst articial, man-made microcapsules
[1,2]. At the same time Cole performed the rst compression experi-
ments on single microcapsules, i.e. on arbacia eggs with a diameter
around 75 m [3]. Especially the development of novel synthesis strat-
egies, e.g., layer-by-layer assembly, and techniques to characterize cap-
sules on a single-capsule level has stimulated scientic research in this
area within the past twenty years. At the same time, microcapsules
have been increasingly used in industry. The rst large-scale production
Corresponding author. Tel.: +49 921 55 2753; fax: +49 921 55 2059.
E-mail address: Andreas.Fery@uni-bayreuth.de (A. Fery).
the 1950s [4]. Today, microcapsules are designed for and employed in
many different elds of application, such as pharmacy [511], food in-
dustry [1222], agriculture [2326], cosmetics [2729], textile industry
[3032], printing [33], biosensor engineering [3436], active coatings
[37,38] and construction [3941]. For instance, in food technology active
ingredients are protected from decomposition through environmental
impacts or avors are prevented from premature volatilization [21].
Textiles have been modied with microcapsules for long-term fra-
grance release, to introduce re retardants and even to combat counter-
feiting [30]. The interest in and the demand for intelligent, custom-
made capsule systems are continuously rising. And scientic research
plays a key role as the understanding of the fundamental properties of
microcapsules is breaking ground for innovation.
2. Microcapsules: denition and assembly strategies
In view of the broad range of capsule systems and the different con-
text in which they have been investigated, it is no surprise that there are
various, sometimes at least partially diverging denitions of the term

0001-8686/$ see front matter 2013 Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.cis.2013.11.016
66 M.P. Neubauer et al. / Advances in Colloid and Interface Science 207 (2014) 6580
microcapsules and microencapsulation [4246]. Therefore, let us rst
clarify the semantics for the purpose of this review: Generally, microen-
capsulation is understood as the process by which one material of
microscopic dimensions is entirely coated by another. Hence, a core-
shell-composite or microcapsule is created where the core can take all
aggregate states but the shell is solid. This fundamental denition al-
ready points out the two main components of microcapsules, core/inte-
rior/inner phase and shell/wall/membrane/outer phase, which can be
tuned with respect to materials, permeability, size, shape etc. Out of
this large variety of possible microcapsules it is indispensable to intro-
duce some further constraints. In the context of this review article we
examine mechanical properties of microcapsules. These are particularly
interesting when dominated by the shell. Therefore, we limit ourselves
to microcapsules being composed of a uid core wrapped by a solid
shell. In contrast, capsules consisting of a solid core will be referred to
as core/shell particles and will not be in the center of interest. In terms
of the mechanical properties of the shell, we limit ourselves to non-
uid shells. The broad class of vesicles formed from lipids or in general
low-molecular weight species will thus not be covered. The microcap-
sules considered in this review will always be spherical, if not stated dif-
ferently, and their size will range from several hundreds of nanometers
to some tens (in few cases to some hundreds) of micrometers, with the
restriction that the shell thickness is small as compared to the diameter.
The focus will nally be on articial microcapsules, which naturally
lets us start from reviewing the various approaches for the formation
of microcapsules meeting the aforesaid denitions. As stated above, mi-
crocapsules nd already various usages in industry. The industrially rel-
evant encapsulation techniques are typically based on physicochemical
processes that allow for large scale production. These include spray
drying [47], co-extrusion, spinning disk, multiple-nozzle spraying,
uidized-bed coating and vacuum encapsulation [42,46]. Among the
advantages of these methods are the easy handling, upscalability and
low costs. On the other hand, the obtained microcapsules are often poly-
disperse in diameter and shell thickness. In other words, current ap-
proaches allow for comparatively little control over the particles
morphology and the possibilities of capsule design are rather restricted.
A far better control over capsule core and shell dimensions and a se-
lective introduction of functionality is provided by template-assisted
and/or self-assembly approaches. Both soft and hard template-assisted
methods offer ne-tuning of the core size and can be combined with a
self-assembly process which allows excellent control over shell thick-
ness, down to molecular level. Soft template-assisted methods are mostly
emulsion-based, such as microuidic processes [4854], polymerosomes
[6,5560] (which are typically nm-sized), colloidosomes [6163], interfa-
cial polymerization [6467], interfacial assembly [68], inkjet printing
[69,70] or phase separation processes [71,72]. A special case is the soft
colloid templated multilayer assembly which offers control over all geo-
metric parameters [73,74]. The underlying principle was rst exploited
using hard templates, namely the layer-by-layer deposition technique
[7580]. Combining templates and self-assembly permits precise adjust-
ment of geometry, diameter [81], shell thickness and shell material [82].
Fig. 2.1. Template-assisted and self-assembly methods for a controlled capsule design. The scheme shows typical wall materials (particles, multilayers, homogeneous lm) and the crucial
geometric parameters, diameter D and wall thickness h.
Furthermore, such methods allow for introduction of multifunctionality
[83]. That means, in addition to enclosing their content until desired de-
livery, microcapsules are designed which, for example in medical appli-
cations, can be tracked within the human body, directed to a specic
site and, nally, specically triggered to release their cargo. A schematic
overview of microcapsule designs obtained from template-assisted and
self-assembly methods is given in Fig. 2.1. It becomes clear that the syn-
thesis process strongly determines the choice of core and shell material,
and the design possibilities.
3. Mechanical characterization of microcapsules
Mechanical properties of microcapsules become accessible through
a variety of experimental techniques. These can be divided into two
general categories: ensemble methods and methods on a single-
capsule level. Ensemble methods measure a batch of capsules simulta-
neously, yielding average values. These measurements can often be per-
formed in an automated, high-throughput fashion and a large number
of capsules are captured. In contrast, single capsule measurements pro-
vide generally more detailed information on deformation properties,
but require a sequential measurement of capsules.
One possibility of determining mechanical properties of microcap-
sule ensembles is to make use of shear forces. A slurry or suspension
of capsules can be measured, for instance, in a turbine reactor [84].
Here, rather high forces are acting provoking breakage of capsules.
Therefore, such a method is mainly relevant for studying large deforma-
tion behavior and release under high stresses. A more sensitive ap-
proach is given by rheological investigations. Drochon et al. measured
the viscosity of a diluted suspension of red blood cells and calculated
the shear elastic modulus of the cell membrane [85,86]. The underlying
model has been derived by the same authors and other groups [8790].
Suspensions of microcapsules under shear have been further studied
experimentally by Bredimas et al. [91] and theoretically by the groups
of Misbah [9296] and Kalluri [97,98].
Another means to obtain information about mechanical parameters
of a multitude of capsules is to perform osmotic pressure experiments.
With the upcoming of polyelectrolyte multilayer capsules (PEMCs)
Gao and co-workers used this method to extract mechanical data
[99,100]. Upon increase of osmotic pressure the capsules started to de-
form and assumed a buckled shape. The onset of this buckling was asso-
ciated with a critical osmotic pressure which was shown to depend on
capsule wall thickness and elastic modulus as well as on the size of
the capsule. The established theoretical model allows for the calculation
of the shells' elastic modulus from the measured critical pressure. In a
later study Datta et al. examined the buckling behavior of Pickering
emulsion droplets by continuously reducing their volume [101]. The re-
sults show that these kinds of capsules undergo similar buckling transi-
tions as known for typical polymer based thin shell systems.
In the following, single capsule measurement techniques will be pre-
sented, ordered according to increasing force sensitivity. Fig. 3.1 gives a
schematic overview. First, we focus on parallel plate compression where
 M.P. Neubauer et al. / Advances in Colloid and Interface Science 207 (2014) 6580
the capsule is deformed between two approaching plates with a typical
force range between N and N. Such studies date back to the early 1930s
when Cole examined surface forces of the arbacia egg with a at gold
wire [3]. Starting from the late 1990s well dened compression of
micron scale capsules was introduced. Zhang et al. developed a micro-
manipulation technique to measure burst forces of melamine formalde-
hyde (MF) microcapsules in a controlled fashion [102]. Fig. 3.2 shows
pictures from a similar deformation experiment. The immobilized mi-
crocapsule is deformed by the at end of a cylindrical probe connected
to a force transducer. The optical microscope allows for alignment and
observation of the deformation in situ. As a result of approaching and
retracting the probe a force versus deformation characteristic is obtain-
ed. Bursting of the capsule is associated with a sharp drop in the record-
ed force. Similar plate compression experiments on MF microcapsules
were conducted by Hu et al. [103], Keller and Sottos investigated
poly(urea-formaldehyde) microcapsules [104]. Theoretical treatment
and simulations can be found in [105107].
A technique closely related to plate compression testing is atomic
force microscopy (AFM). Similar to the situation in a micromanipulator
uniaxial deformations are effected, however, the accessible force range
is shifted to smaller values (pN to N) accompanied with higher resolu-
tion [109]. Therefore, it is a suitable tool for capsule systems to study
shell mechanical properties in the small deformation regime on the
order of the shell thickness. Often, the colloidal probe setup is used,
where a particle of colloidal dimensions is attached to a tip-less cantile-
ver to achieve well dened spheresphere deformation geometry. In
analogy to plate compression AFM can be combined with optics and
measurements in air and in liquid are feasible. With the help of reec-
tion interference contrast microscopy (RICM) the simultaneous obser-
vation of the capsule's contact area with the substrate while
performing a deformation experiment becomes possible. Fig. 3.3 depicts
a typical force vs. deformation characteristic from a colloidal probe AFM
measurement including the corresponding RICM images. First studies
with the colloidal probe technique to characterize PEMCs were reported
independently from Vinogradova and co-workers [110112] and from
Fery and co-workers [113115]. The elastic modulus of PSS/PAH multi-
layer capsule shells was determined to be in the low GPa range. It was
shown that the shell thickness has a drastic inuence on the mechanical
properties. Further, by using an optical microscope in RICM mode it was
possible to reconstruct the actual capsule shape both in undeformed
state and during measurement. Other groups have employed the colloi-
dal probe technique to study mechanical properties of vesicles [116], MF
Fig. 3.1. Schematic representation of single-capsule measurement techniques, each with typically available force range. Arrows indicate the directions in which forces are acting.
67
capsules [117] and biopolymer capsules [118] or the salt softening of
PEMCs [119]. Shell mechanical properties of capsule systems can equal-
ly be investigated by AFM when using a cantilever with a sharp tip at
its apex. However, measurements have to be performed carefully
avoiding penetration of the shell. Consequently, the applicable force
range is typically lower than with a colloidal probe. A variety of systems
has been tested with this method, such as vesicles [120,121], polymeric
capsules [122], capsules with a silica shell [123], viral shells [124,125]
and polymersomes [126]. A third option for capsule deformation with
AFM is to employ a tip-less cantilever. Here, the major constraint arises
from the fact that commercially available cantilever holders are tilted by
several degrees; a typical inclination angle is 10. Therefore, compres-
sion will always be accompanied by some shearing or sliding, which
can lead to pushing away the capsule in extreme cases. Yet, for moder-
ate loads and small capsules (with respect to cantilever dimensions)
these effects should be acceptably low. With this method a range of mi-
crocapsules and - bubbles has been investigated [127131].
A conceptually completely different approach is to apply shear stress-
es. The typical range of these stresses is from mPa to kPa, i.e. for capsules
with a typical radius of 5 m the applied forces can be estimated to be in
between 0.1 pN and 0.1 N. Several studies have been performed in
Couette ow, i.e. the microcapsules are exposed to shear ow created
by two concentric cylinders rotating in opposite direction [132136].
The outer cylinder of the rheoscope is optically transparent, thus en-
abling observation of capsule shape and orientation with a microscope.
An example is given in Fig. 3.4, where the shear rate has been increased
until capsule break. A similar setup is used for spinning drop experi-
ments [137142]. Here, the microcapsule is placed within a liquid lled
rotating tube and shape changes are again followed via microscope. In
both methods, the shear modulus is determined, based on the change
in capsule shape as a function of applied shear forces. Theoretical models
for different shear and ow conditions have been developed [143149].
A related method is based on microuidics. The microcapsules mechan-
ical properties are studied by guiding them through narrow channels
and following the change in shape. Such an approach has been reported
both for biological cells [150] and articial capsules [151154]. Corre-
sponding theoretical descriptions have been worked out [155162].
A more sensitive technique is micropipette aspiration. It has origi-
nally been developed by Mitchison and Swann to examine elastic
properties of living cells and the setup was therefore termed cell
elastimeter [163]. A glass micropipette is connected to a movable res-
ervoir which effects slight suction when lowered. In this way a single
68 M.P. Neubauer et al. / Advances in Colloid and Interface Science 207 (2014) 6580
Fig. 3.2. Sequence of images of an alginate capsule under parallel plate compression with a micromanipulator. Image adapted from [108]. Copyright 2003 Wiley. Used with permission
from Carin et al., Compression of biocompatible liquid-lled HSA-alginate capsules: Determination of the membrane mechanical properties, Biotechnology & Bioengineering, John
Wiley and Sons.
cell can be aspirated, held and depending on the position of the reser-
voir suction pressure can be systematically varied and capsules can be
released after the experiments. Normally, applied pressures range be-
tween 1 Pa and 1 kPa. This means, with typical inner diameters of the
capillary of 15 m, forces in between pN to nN are exerted. Shape
changes of the capsule are followed with an optical microscope (see
Fig. 3.5). The observed bulging of the cell membrane is used to extract
information about mechanical properties such as stiffness, Young's
modulus or internal pressure. Since these rst pioneering contributions
the technique has been improved further and applied to study both bi-
ological samples [164169] and articial capsules [170173]. Theoreti-
cal models have been developed to accurately describe and evaluate
micropipette aspiration experiments [167,174180].
Finally, a class of methods is discussed which enables the exertion of
very low forces (several tens of fN to some hundreds of pN): optical and
magnetic tweezers. Though mainly used to study biological samples
(e.g., cells) we still add this paragraph to round out the picture
concerning single-capsule deformation techniques. Generally, optical
tweezers exploit the forces arising from a light source such that a dielec-
tric particle can be trapped and manipulated. Detailed information
about this technique and theoretical background can be found in
[181185]. In a classical experiment two beads which are attached to
opposite sides of a cell are trapped with optical tweezers and then pulled
apart to investigate the cells mechanical properties and determine elas-
tic parameters such as the shear modulus of the cell membrane
[186188]. An example is given in Fig. 3.6, where the experimental
Fig. 3.3. Force-deformation characteristic of a polyelectrolyte multilayer microcapsule,
10 m in radius. Insets show corresponding RICM micrographs. A clear correlation can
be observed between applied loads and apparent contact area [113]. Buckling of the
shell is evidenced by discontinuities in the curve and, correspondingly, abrupt changes
in contact geometry. With kind permission from Springer Science and Business Media:
Springer, the European Physical Journal E, 12 (2), 2003, p.215, Elastic properties of poly-
electrolyte capsules studied by atomic force microscopy and RICM, F. Dubreuil, Fig. 4.
observations are accompanied by numerical simulations. Non-
symmetric systems with only one traceable particle attached to a cell
have been studied by Titushkin et al. [189] and by Frases and co-
workers [190]. Calibration of optical tweezers has been treated in the
group of Nussenzveig [191,192]. A special case of optical tweezers is
given in the optical stretcher where microcapsules can be directly
trapped and deformed without additional particles. This method was in-
troduced by Guck et al. [193], theoretical considerations can be found in
[194196]. The working principle of magnetic tweezers is similar to op-
tical tweezers. Magnetic beads attached to a cell wall are trapped in a
magnetic eld and then moved to perform a microrheology experiment
[197199].
4. Modeling physics of capsule deformation
As it was shown in the previous part a wide range of techniques has
been established to characterize mechanical properties of capsule sys-
tems. There are static, quasi-static and dynamic methods which all
need to be evaluated with a suitable physical model to extract meaning-
ful quantities out of the obtained data. As compared to the deformation
of massive particles made from an elastically homogeneous medium,
modeling capsule deformation is intrinsically more challenging and
qualitatively new features arise, which are often linked to nonlinear ef-
fects. In addition, several qualitatively different deformation regimes
are found. Deformations can be on the same range or small as compared
to the capsules' typical length scales such as wall thickness or radius,
and capsules can be permeable or not, to mention only the most impor-
tant aspects. In the following we rst focus on the (more general)
modeling of capsule deformation within the framework of shell theory
before comparing to membrane approach and discussing more complex
deformation scenarios.
Shell structures are widely and successfully used in nature, architec-
ture and technology, covering all length scales in-between biological
cells and dome constructions [201]. However, the underlying physical
concepts to describe their mechanical properties and to predict re-
sponse to applied loads are the same. One of the major advantages of
shells is that, despite often being very thin and thereby saving material,
extreme stability and protection of the interior are nevertheless guaran-
teed. This brings us to a rst important (and for many systems valid)
simplication concerning theoretical treatment: the restriction to thin
shells, i.e. structures with a shell thickness h to radius R ratio of less
than 1/20 [202]. Here, R corresponds to the radius of curvature of the
middle surface between the inward and outward faces of the shell. In
the course of this section shells will always be considered as thin. Fur-
ther assumptions in thin shell theory are linear elasticity of the shell ma-
terial (which is supposed to be homogeneous and isotropic), small
deformation with respect to the shell thickness, and the Kirchhoff hy-
potheses (constant shell thickness, neglect of transverse normal stress
and in-plane shear), together known as the KirchhoffLove assump-
tions. Additionally, the 3D-shell-problem is reduced to a 2D-problem
by focusing on the middle surface of the shell [202]. One of the rst sci-
entists to present such a rst-order approximation was Reissner
 M.P. Neubauer et al. / Advances in Colloid and Interface Science 207 (2014) 6580 69

Fig. 3.4. Series of images of an initially spherical polysiloxane microcapsule in shear ow at different shear rates until break. Reproduced from [136] with permission of The Royal Society
of Chemistry (RSC).

[203207]. His analysis revealed a linear scaling of applied force F and
resulting deformation d.
h2 4E
F  q
   d:
R 3 1v2
Further variables in Eq. (1) are the radius of curvature R, shell thick-
ness h and the material elastic constants, Young's modulus E and
Poisson's ratio . Originally developed for point loads, Reissner's theory
has been experimentally proved to be valid also for less concentrated
loading situations, e.g., deformations with a colloidal probe [109]. In
the context of microcapsules this simple result is particularly interesting
as the shells' elasticity modulus becomes directly accessible from small
deformation experiments, e.g., parallel plate compression or AFM force
spectroscopy. An overview over further rst- and higher-order approx-
imations is provided in [202].
A constraint to the simple description of small deformations can
arise from membrane pre-tensions which become important for very
thin shells. In a pioneering work, Ferri and co-workers tried to separate
the contributions of surface tension and mechanical membrane tension
to the overall deformation behavior of Pickering emulsion droplets
[208]. A model was developed accounting for both tension contribu-
1 tions and including the shape changes of the capsule during compres-
sion. Based on experimental data, stressstrain relations are calculated
and compared to the predictions of continuum mechanical shell models.
Signicant differences are found which are attributed to strong inu-
ence of surface tension effects originating from the oilparticlewater
interface. Tan et al. built up on this work and investigated mechanical
properties of droplets stabilized by clay particles [209]. Predictions
from Ferri's work are in good agreement with their experiments. As
the determined surface Young's modulus depends on the applied strain,
it is clear that the shells' elasticity cannot be described by a pure Hook
law. This non-Hookean behavior is, again, suggested to result from in-
terfacial tensions.
Pre-ination as it can arise from swelling has been identied as an-
other source of pre-tension. It has been shown that the shape of cap-
sules in axisymmetric ow is largely inuenced by such additional

Fig. 3.5. Micropipette suction experiment with a polymersome. After aspiration (a) and collapse (b) a positive pressure is applied (c), nally leading to full recovery of the capsule (d). Scale
bar is 5 m. Reproduced from [173] with permission of The Royal Society of Chemistry (RSC).
70 M.P. Neubauer et al. / Advances in Colloid and Interface Science 207 (2014) 6580

Fig. 3.6. Cell deformation experiments with optical tweezers at increasing loads. Left, optical micrographs, right, corresponding simulations revealing strain distributions and 3D-shape
changes. [200] Reprinted from Acta Materialia, 52, C.T. Lim et al., Large deformation of living cells using laser traps, Copyright (2004) with permission from Elsevier.

mechanic tension [162]. A corresponding trend was found for capsules [220,221] a model is presented where the critical osmotic pressure is re-
in shear ow. Here, the deformation characteristic is signicantly al- lated to the elastic modulus of the shell.
tered and, for high pre-stresses, the validity of small deformation theory
is passed [148].  2
2E h
Remaining under thin shell assumptions we now focus on larger de- pc q
  : 3
3 1v 2 R
formations. For the simplest case, a capsule with innite permeability,
Pogorelov proposed the following relationship for a Hookean material
under point load [210]

1:89Eh2 p
F   hd: 2
R 1v2

In this scenario, a dimple is forming and, in contrast to Reissner's for-

mula, the force no longer scales linearly but with the square root of de-
formation. Theoretical solutions of the large deformation problem
under assumption of non-Hookean models, such as Neo-Hookean or
MooneyRivlin, are presented in [211,212]. These hyperelastic material
models are used to describe the nonlinear stressstrain relation beyond
Hookean elasticity. Here, effects such as yielding and thinning of
the shell become important. Rachik et al. compare 3D (Neo-Hook,
MooneyRivlin, Yeoh) with 2D constitutive models (STZC, Evans-
Skalak) [105]. Generally, they nd that all investigated models (except
for the Neo-Hookean) t the experimental data well. However, a
concluding recommendation which model to choose could not be
given. One crucial parameter to consider will be the shell material's
properties, e.g. whether strain-hardening or -softening occurs at large
deformations [213,214].
Several studies have used the onset of buckling, as described by
Pogorelov, as a means for estimating elastic properties of shells
[215219]. Experimentally, this can be addressed by using osmotic
Fig. 4.1. Buckling of polyelectrolyte multilayer capsules induced by osmotic pressure [99].
pressure effects. For instance, Gao and co-workers made use of the os- With kind permission from Springer Science and Business Media: Springer, the European
motic pressure to calculate the elastic modulus of PSS/PAH polyelectro- Physical Journal E, 5 (1), 2001, p.21, Elasticity of hollow polyelectrolyte capsules prepared
lyte capsules (see also Fig. 4.1) [99]. Following earlier argumentations by the layer-by-layer technique, C. Dubreuil, Fig. 2b.
 M.P. Neubauer et al. / Advances in Colloid and Interface Science 207 (2014) 6580 71

Here, pc is the critical pressure when buckling of the shell starts. This
pressure scales directly with the shell thickness squared and indirectly
with the square of radius, or, in other words, pc scales indirectly with
the Fpplvon Krmn number .
 R2
2
12 1v : 4
h

The experimental data clearly conrmed this relation and the deter-
mined modulus is in good agreement with independent measurements
[113]. Vliegenthart and Gompper analyzed the problem of capsule
buckling under external pressure by means of simulations [222]. They
found that the shape of the capsules in the deformed state is determined
by three variables, deformation rate, reduced volume and, again, the
Fpplvon Krmn number .
The simulations reveal two energy regimes. The rst, for small in-
dentations with circular dimple, follows the classic prediction after Lan-
dau and Lifshitz with the energy scaling like E 1/4 [223]. When the
shell is deformed to a larger extend leading to polygonal shape of the
dimple, the scaling exponent changes to less than 1/6.
Generally, the formation of a dimple or invagination upon large de-
formation of capsules has received much attention in the literature.
Buckling instabilities have been observed and described in both experi-
mental and theoretical studies [224242]. Special cases are pressurized
shells which show wrinkling under point load conditions [243]. The
same group has also studied the mechanical properties of pressurized
shells under point loads [244]. In addition to the initial linear regime
as predicted by Reissner for small deformations a second linear regime
was found for large indentations.
It is obvious that for a range of systems, particularly for large defor-
mations, permeability is not negligible and, therefore, needs to be
considered. For small deformations of a capsule, irrespective of perme-
ability, the force F scales linearly with relative deformation (deforma-
tion divided by capsule radius R) [245].
4 2
F Eh
3 limit of compliant shells as has been outlined above or, in general, for
This is the basis for Reissner's reasoning. In the case of an imperme-
able membrane an additional term has to be considered. This term ac-
counts for the stretching of the shell while being deformed. Here, the
force scales cubically with deformation [111]
16 3
F EhR :
3 membranes or lipid bilayers. The bending resistance of such membranes
Hence, the complete description of the deformation of an imperme-
able capsule is given by the sum of Eqs. (2) and (3). Plotting both scaling
laws in a common graph (Fig. 4.2) shows clearly that, as long as we
restrict ourselves to small deformations on the order of the shell
thickness, permeability issues are negligible. In contrast, for large defor-
mations volume-constraint contributions become increasingly domi-
nant. Therefore, capsule wall permeability has to be considered in
modeling of large deformations.
In this case, additional contributions arise particularly from edge
bending at the sites of high curvature around the dimple and stretching
caused by the rising uid pressure [246]. Comparing both experimental
data and theoretical calculations for the deformation of an empty and a
water-lled racquetball Taber found that deformations below 20%
are dominated by bending. Only for larger compression the load-
deection curve of lled shells deviated from the square root like scaling
and compared to the empty shells a stiffening was observed [246].
Finally, at very high loads capsule burst can occur. Experimentally,
Zhang et al. found for melamine formaldehyde (MF) microcapsules a
clear correlation with both bursting force and displacement at burst in-
creasing in a linear fashion with capsule diameter [102]. Additionally,
it was discovered that burst typically occurs at a critical relative
Fig. 4.2. Linear elastic (continuous line) and volume-constraint (dotted line) contributions
to forces F upon capsule deformation (relative deformation ), calculated for a capsule
10 m in diameter, shell thickness of 20 nm and Young's modulus of 1 GPa.
deformation of 70%, irrespective of capsule size [247]. Mercad-Prieto
et al. carried out nite element modeling (FEM) to elucidate the failure
behavior of MF microcapsules [106]. The compression behavior be-
tween two parallel plates is simulated up to bursting by applying an
elastic-perfectly plastic model with strain hardening and comparison
with experimental data shows very good agreement. Strain at rupture
for this system was found to be approximately 0.48 and a failure stress
of around 350 MPa was obtained.
After going through thin shell theory it is worth considering a special
type of thin shell, which has often been treated in the literature: the
membrane. Generally, shell structures support externally applied
loads in two ways: in-plane (stretching and shear) and out-of-plane
(bending and twisting) [109,202]. Thus, we can imagine two extreme
cases. For very stiff, solid shells the out-of-plane mode can be largely
neglected. The stability of these shells originates from their high resis-
tance to bending just imagine the huge dome constructions in archi-
tecture or the stiffness of an egg shell [202]. Accordingly, these thin
shells carry axial loads almost exclusively by in-plane action. In contrast,
stretching or shear can be neglected either in the small deformation
5
a special shell design. The particular architecture of uid membranes al-
lows for translational displacements of the constituting layers at
vanishing energy cost. At the same time, bending and twisting moments
are small, i.e. the main mechanical characteristic of a uid membrane is
its exibility. It supports external loads only by its tension and deforms
in pure bending [202,248]. Such conditions are often fullled in biolog-
ical systems. Surely, the prototypes of uid membranes are cellular
6
has been treated in a range of publications [248254]. The key variable
to describe mechanical properties of membranes is the bending rigidity
kbend. It is related to the area elastic modulus KA by a simple expression
[250,255]:
2
kbend K A h : 7
Here, is a constant and h is again the membrane thickness. The
bending rigidity is typically given in multiples of kBT in order to com-
pare the stability of the extremely compliant membrane to the thermal
energy, which may be sufcient to induce uctuations. However, there
is also a class of membrane-like systems with nite shear modulus, i.e.
in-plane elastic energy has to be considered. In the literature, these
are commonly referred to as tethered or polymerized membranes
[248,249,252]. Here, the shell consists of a (partly) interconnected net-
work instead of a loose assembly of individual molecules in two distinct
layers. Several studies described such membrane-like systems including
both bending and shear contributions [253,254,256]. That means we
are back in an intermediate regime where both in-plane and out-of-
plane contributions have to be accounted for in physical modeling.
Hence, when a uid membrane is properly modied (cross-linked,
72 M.P. Neubauer et al. / Advances in Colloid and Interface Science 207 (2014) 6580
strengthened), a transition is observed towards the universal shell-like
behavior. In other words, the shell material sets the boundary condi-
tions for the correct interpretation of mechanical data. In order to better
capture transitory states or limiting cases Simmonds et al. suggest in
their theoretical analysis to describe a spherical shell under load by
the sum of a membrane-like, a shell-like and a slab-like solution [257].
This way, simplications of the KirchhoffLove thin shell theory and er-
rors resulting thereof should be overcome. Another theoretical treat-
ment of a capsule's wall mechanical properties in-between the state of
uid membranes and solid shells is presented by Tu and co-workers
[258].
While mainly axial deformation has been considered so far we now
turn to a more complex scenario, namely capsules in (shear) ow. A re-
cent overview of this topic can be found in [146]. In the simplest case, a
homogeneous thin elastic shell is modeled following Hooke's law for
small deformations. It is characterized by its surface shear modulus GS
and area dilation modulus KS, with KS = GS(1 + )/(1 ) and
being the Poisson's ratio. The principle tensions T1,2 and extension ratios
1,2 are correlated to give the subsequent equations:
GS h 2 
2
i
T1 1 v 2 1
1v 1
GS h 2 
2
i
T2 2 1 v 1 1 :
1v
More details on freely suspended microcapsules in simple shear ow
can be found in a range of publications [8789,143] covering also tum-
bling [145,147,259], large deformations [90] or the effect of pre-stresses
[148]. A closely related topic is the motion of capsules in channels, e.g.,
blood cells or delivery vehicles in arteries. Several groups have ad-
dressed this issue [155162]. When a capsule ows through a constric-
tion it assumes a certain shape depending on its mechanical properties,
ow rate, channel size [155] and geometry [157,158].
To conclude this section we would like to draw the readers' attention
to some examples of non-spherical capsules. Delorme and co-workers
studied the mechanical properties of polyhedrons [260]. Both the elastic
modulus (Reissner approximation for thin shells) and bending modulus
(membrane theory) were determined and found to be in a reasonable
range compared to independent measurements. Additionally, a distinct
difference in stiffness between facets and vertexes could be shown. The
Fig. 4.3. a) Ellipsoidal shells with different aspect ratios b/a. b) Effect of aspect ratio on force-deformation characteristic for axial loads on non-pressurized shells. c) Effect of internal
pressure for a given aspect ratio (1.5). Pressure ranges from 0 to 10 kPa.[261] Copyright (2012) by the American Physical Society.
mechanical properties of ellipsoidal shells are studied in [261] and
[262]. It is clearly shown how geometry, namely the curvature, inu-
ences the stiffness of a given shell, e.g., that a hen's egg supports higher
loads at its poles than around the equator. Additionally, the stiffening ef-
fect of internal pressure is examined (see Fig. 4.3).
Another class of non-spherical microcontainers, capsids, is investi-
gated in [263]. The authors present a corresponding elasticity theory
and reveal the interrelation between energy and shape. This nally
leads to a shape phase diagram, where the transitions from spherical
to spherocylindrical to icosahedral geometries are given as a function
of the spontaneous curvature and the Fpplvon Krmn number. Me-
chanical properties of hollow tubes have been characterized and evalu-
ated by Mueller et al. [81,264], based on a model developed earlier for
microtubules [265]. The scaling of the tube wall materials' stiffness
with wall thickness and radius is similar to the Reissner relation for
spherical shells, yet with slightly higher exponents. Anisotropic micro-
capsules assuming cubic or pyramidal shapes were constructed via a
layer-by-layer approach by Shchepelina and co-workers [266]. With
the help of computer simulations it is demonstrated that these geome-
tries provide enhanced mechanical properties compared to spherical
capsules. Simulating osmotic pressure, the edges and corners, i.e. the re-
8
gions of high curvature, act as a kind of intrinsic frame which stabilizes
the whole structure, whereas the hollow spheres show the typical buck-
ling instabilities. In a later work, hollow cubic capsules are investigated
9
with regard to pH-induced shape changes [267]. While (PMAA)20 cap-
sules show a shape transition to spherical structures, the (PMAA-
PVPON)5 capsules retain their morphology. This difference is attributed
to a change in materials' stiffness. The more rigid composite better with-
stands the stresses due to pH triggered swelling, whereas the softer
single-component capsule is subject to bending of its side faces.
Generally, numerical methods such as nite element modeling
(FEM) can help to understand experimental observations and to predict
system response, particularly when more complex morphologies are in-
vestigated (e.g., the anisotropic capsules discussed before) and when
deformation regimes beyond linear elasticity are probed (e.g., capsule
burst). In these cases analytical treatment is often not possible. In FEM
simulations the shell is modeled as consisting of a nite number of dis-
crete elements [268270]. With this approach several capsule systems
have been studied, e.g., articial spherical capsules [105107,271274]
and icosahedral viral capsids [275278]. An alternative way to reduce
complexity is to model the shell structures as spring networks. Here,
 M.P. Neubauer et al. / Advances in Colloid and Interface Science 207 (2014) 6580
the continuous shell is replaced by a grid with a set mesh size where the
links between the nodes represent springs obeying a predened elastic-
ity law. This model has been shown to apply well to both icosahedral
[237,279281] and spherical shells [222]. A related approach is coarse-
grained simulation techniques [282285] and meso-scale modeling
[286,287]. Instead of considering every single atom or molecule as in
classical molecular dynamics simulations (which is far too time-
consuming for micron-sized systems) several molecules or polymer
segments are grouped and represented by one bead. Neighboring
beads are connected by a bond to which a certain potential is attributed.
Several groups employed this technique to examine mechanical proper-
ties of microcapsules [286,288290] and viral capsids [278,291293].
5. Functionality and application perspectives
As has been outlined in the introductory section microencapsulation
is already today an important processing method in industry and bears
great potential for a wide range of applications. Mechanics of microcap-
sules plays a critical role for the ultimate purpose of most encapsulation
applications: controlling release of the encapsulated material. Depend-
ing on the specic application, desired release scenarios range from
prolonged release by diffusion through the capsule wall to quick burst
release. For the rst scenario, mechanical failure of microcapsules will
result in premature release and has to be avoided by designing micro-
capsules in a way that they withstand the wear and tear associated to
storage, transport and administration. For the second scenario, mechan-
ical failure can become a powerful release mechanism, if mechanical
properties can be designed such, that instabilities occur under the de-
sired conditions. Thus it is no surprise, that recent patent literature
puts strong emphasis on mechanical properties [294,295].
In the light of the previous chapters, it is evident that especially con-
trolling mechanical instabilities requires excellent control over relevant
geometrical parameters of the microcapsules. For spherical systems
these are radius and wall thickness. Therefore, template assisted
methods like LBL greatly extend the possibilities, since the radius can
be well adjusted using monodisperse templates and wall thicknesses
can be controlled on the molecular scale. In the following we will illus-
trate this using some examples from recent literature focusing on
PEMCs without claiming complete coverage of the broad eld of
microcapsules.
While mechanical experiments on PEMCs have rst focused on esti-
mating the Young's modulus and its responsiveness towards external
parameters like temperature [296,297], pH [298,299] and salt-
concentration [119,299,300], so far the correlation between mechanical
properties and release of encapsulated material has received little atten-
tion in this eld. Fernandes et al. studied the release of a uorescent dye
from microcapsules as a function of deformation by colloidal probe AFM
(Fig. 5.1).[301] The change of uorescence intensity within the micro-
capsule was followed and a clear correlation between deformation
and uorescence intensity of encapsulated dye was observed. Interest-
ingly, a sharp drop in intensity occurred at a relative deformation
around 20%, which could be attributed to a transition from an elastic
to a plastic deformation regime indicating mechanical failure at this
point.
Similar studies were carried out by Palankar et al. who investigated
the release of biodegradable polymer microcapsules upon mechanical
deformation ex situ and their uptake by HeLa cells in vivo [118]. The
technique opens the possibility to quantify forces for mechanical failure
in a force regime several orders of magnitude below conventional in-
dentation tests. An example for the relevance of this force regime
can be found in recent studies of cellular uptake of microcapsules
[302,303]. The uptake process is accompanied by forces that are exerted
on the microcapsule. If these forces are high enough to induce mechan-
ical instability, encapsulated material will be released prematurely and
not enter the intracellular area. The authors showed, using a series
of microcapsules with varying deformability, that there is a clear
73
Fig. 5.1. Fluorescence intensity as a function of relative deformation of a microcapsule
(lled symbols) and control experiment (open symbols) with a microcapsule not subject-
ed to deformation. Insets show corresponding images of a microcapsule at different
degrees of deformation as indicated by arrows. Scale bar is 5 m. Reproduced from
[301] with permission of The Royal Society of Chemistry.
correlation between microcapsule mechanics and the probability of
release during the uptake process (see Fig. 5.2). Apart from the rele-
vance for intra-cellular delivery it was possible to estimate the forces
that the cell wall exerts during incorporation. Thus mechanically well-
dened microcapsules could serve as probes.
However, the relevance of deformation properties for cellular uptake
goes beyond these stability considerations. Several studies showed that
mechanical properties as well inuence the uptake probability signi-
cantly; yet, these studies investigated full instead of hollow spheres.
Beningo et al. found that bone-marrow-derived macrophages from
mice preferred harder particles to softer ones [305]. Here, the stiffness
of polyacrylamide beads was tuned by changing the amount of
crosslinker resulting in a more than threefold difference in modulus
(absolute values were not given). In contrast, Liu et al. found that
HepG2 cells internalized softer particles faster and to a greater extent
than the stiffer ones [306]. Here, particles consisted of poly(2-
hydroxyethyl methacrylate) (HEMA) and, again, the modulus was
tuned by varying crosslinker content (compressive modulus from 15
to 156 kPa). Banquy et al. discovered that the stiffness of particles
from the same material and similar modulus range had an inuence
on the pathway how they are taken up by murine macrophage cells
[307]. In a theoretical study Yi et al. show the wrapping of a vesicle by
a cell membrane [308]. It is stated that due to energetical reasons, up-
take of stiffer particles is preferred. While the different ndings suggest
that there is no simple design criterion for all cell types, the signicance
of deformability is central. Generally, the possibility to now prepare mi-
crocapsules with well-dened mechanics, study their properties on sin-
gle particle level and correlate them with cellular uptake should provide
the basis for gaining understanding of this behavior and for examining
mechanical responsiveness for the uptake.
While in the above examples, mechanical instability was due to an
external force, PEMCs have as well been used to show burst release
due to internal forces: Since their shells are semi-permeable, osmotic
pressure provides a means for causing tension and eventually collapse
or bursting of microcapsules [100]. This has been taken advantage
of for programming the mechanical instability of microcapsules:
De Geest and coworkers deposited an LbL shell onto hydrolyzable
hydrogel-cores [309,310]. The system is designed such, that the shell
is impermeable for degradation products of the dextran-based gels.
Thus increasing osmotic pressure can build up in the course of gel hy-
drolysis and trigger capsule-burst [311]. Mechanical stability and resis-
tance towards osmotic pressure can be tuned by adjusting the
composition and thickness of the capsule wall. Thus tailored release
74 M.P. Neubauer et al. / Advances in Colloid and Interface Science 207 (2014) 6580

Fig. 5.2. Release from microcapsules with different mechanical strength depending on annealing temperature. (a) Soft capsules release the uorescently labeled encapsulate prematurely,
i.e. outside the cell. The more rigid capsule is entirely uptaken without rupturing. b) Release as a function of applied force and deformation from single capsule measurements.[304] Copy-
right (2010) Wiley. Used with permission from Delcea et al., Mechanobiology: Correlation between mechanical stability of microcapsules studied by AFM and impact of cell-induced
stresses, Small, John Wiley and Sons.

can be achieved covering timescales between seconds and days (see
example of fast response in Fig. 5.3) [312].
This is particularly useful for pharmaceutical applications like vacci-
nation, where a sustained delivery of vaccines is desired. This can now
be realized by a single vaccination with a cocktail of microcapsules
displaying different, temporally tuned release proles [313]. An inter-
esting aspect of the burst release that is visible in Fig. 5.3 is its direction-
ality. Membrane failure occurs usually at a single point only, and the
expulsion of the encapsulate is driven by the ows induced by the relax-
ation of the pressure difference. Therefore, release is not a diffusion con-
trolled process in this case. Knowing the weak points of the membrane
where mechanical instability occurs, the location of release can be
predetermined; experimentally, defects or destabilizing elements can
be included and addressed externally [314]. Deformation experiments
have been carried out to elucidate the mechanical properties and their
relevance for release for this class of microcapsules [315]. In this con-
text, using non-spherical microcapsules offers interesting perspectives.
As shown by Tsukruk et al., cubic or tetrahedral microcapsules exhibit
non-trivial rupture spots at the edges/corners where strains are local-
ized [266]. This opens the way towards directed release applications.
While in the previous examples mechanical stability was investigated
in a quasi-static deformation regime at low frequencies, high frequency
mechanics of microcapsules have also caught much attention recently:
Especially Ultrasound (US) is of broad interest, since ultrasound is widely

Fig. 5.3. Confocal microscopy images of LbL-coated microgels at different times. At 0 s sodium hydroxide is added leading to capsule burst and release of uorescent dye after 10 s. Scale bar
unit is m [312]. Reprinted with permission from the Journal of the American Chemical Society, 130, 14480, De Geest et.al, Microcapsules ejecting nanosized species into the environment.
Copyright (2008) American Chemical Society.
 M.P. Neubauer et al. / Advances in Colloid and Interface Science 207 (2014) 6580
Fig. 5.4. The anisotropic shape of polymer vesicles after a buckling transition is exploited for forming articial stomatocytes and facilitating active motion on the colloidal scale: Catalytic
platinum nanoparticles are introduced into the cavity and oxygen generated by decomposition of hydrogen peroxide results in propulsion. Reprinted by permission from Macmillian
Publishers Ltd: Nature Chemistry, [330], copyright (2012).
used in medical diagnostics and therapies. Thus, microcapsules carrying
therapeutic gases could depending on US intensity do both enhance
contrast and systematically release of therapeutically active gases. The
applied US intensities strongly determine the microcapsules response.
For gas-lled microcapsules the acoustic response can typically be divid-
ed in three regimes: 1) linear oscillations for low-ultrasound intensities
2) non-linear oscillations also called harmonics for increased US intensi-
ties and 3) the fragmentation of microcapsules when a certain pressure
threshold is reached [316]. Theoretical descriptions of the dynamic linear
and non-linear deformation observed in experiments are discussed with
regard to shell properties and the microcapsule length scales, radius and
shell thickness for example in [317] and [318]. Recently, we showed for
polymeric gas-lled microcapsules the change of low and high frequency
mechanics upon integration of nanoparticles in the shell [319].
Theranostic concepts such as US diagnosis combined with the release
of therapeutic NO gases by high-intensity ultrasound or alternating mag-
netic elds were recently reported by different authors [320,321]. How-
ever, oscillation of microcapsules during ultrasound exposure is
restricted to gas-lled microcapsules with thin soft shells. For other de-
signs of microcapsules, effects such as cavitation, the formation of small
bubbles in the liquid medium, and thermal effects can be used to release
therapeutics stored in liquid-lled microcapsules [322].
Shchukin and co-workers were among the rst to investigate US-
triggered release from PEMCs [323]. It could be shown that embedding
of nanoparticles into the shell increases the sensitivity towards US. This
effect could be attributed to both nanoparticle induced shell stiffening
[324] raising the brittleness of the material and a higher density gradi-
ent which locally enhances US action. In later studies the correlation
between shell thickness, amount of embedded nanoparticles and resis-
tance against ultrasonic treatment were elucidated to more detail for
PEMCs and polymer-shelled microcapsules [325327]. Interestingly,
while theory suggests and earlier studies on PEMCs found an increase
of capsule stiffness with shell thickness [113,325], Kolesnikova et al. ob-
served a decrease in stiffness and elastic modulus with increasing shell
thickness and amount of included nanoparticles [325]. Obviously, in this
system the introduction of NPs makes the shell fragile, which is
reected by an increased sensitivity towards US.
The mechanical instability of microcapsules can also be used to in-
duce shape changes/break the spherical symmetry of capsules. As has
been shown in the previous chapter capsule deformations are often ac-
companied by buckling, particularly for large compressions. Control
over this process offers an elegant and simple way for the production
of anisotropic particles with a multiplicity of available geometries. This
is of great interest especially in the eld of materials science, e.g., with
regard to plasmonics or meta-materials, when tailored morphology is
combined with directed assembly. Quilliet and co-workers present ex-
perimental and theoretical studies on non-trivial buckling [240]. They
show that buckling can be easily induced by the removal of solvent
from the capsules' interior in order to give a variety of anisotropic
shapes. These geometries depend mainly on the shell properties, in
75
particular the Fpplvon Krmn number. A similar approach was
adopted by Datta et al. for particle coated droplets [101]. The same
group illustrated the drastic inuence of inhomogeneities on the buck-
ling process which could provide another means for tuning shapes
[231]. Combining both buckling and assembly of sub-micron sized poly-
meric capsules was described by Yang and co-workers [328]. First, hex-
agonally packed 2D-arrays were created by convective self-assembly
and then shape changes were induced via solvent evaporation. A similar
approach has been reported recently by Zhang et al. for core-shell parti-
cles [329]. An interesting advancement for the application of non-
spherical capsules has been published recently by Wilson and co-
workers [330]. Bowl-shaped micro-containers were produced by the
controlled buckling of polymer vesicles to serve as moveable articial
stomatocytes. Softer anisotropic capsules were formed using osmotic
pressure induced buckling, and their cavity was lled with catalytically
active platinum nanoparticles turning hydrogen peroxide (which is
present in the medium around the capsules) into oxygen and water.
The oxygen produced inside the cavity escapes through the opening of
the stomatocyte and, thereby, creates a pressure that is sufcient to pro-
pel the capsule in the opposite direction (Fig. 5.4).
Finally, adhesion is a crucial parameter for many applications of cap-
sule systems. In the biological or medical domain it is important to
know, understand, and eventually, modify or trigger adhesive interac-
tions. For example, the adhesion between a capsular delivery container
and target cells supposed to take up the cargo should be promoted spe-
cically. On the other hand, adhesion may also not be desired, for in-
stance, when capsules are intended to circulate for a longer period of
time in blood vessels (e.g., for purposes of imaging or sustained release).
Elsner et al. investigated the inuence of shell thickness on adhesion
[331]. It turned out that with increasing number of PE layers (which
also means an increase in mechanical stability) adhesion of the capsules
to the substrate decreased as monitored by the contact radius. Two de-
formation scenarios were distinguished based on which the scaling of
contact radius along with shell thickness and radius could be predicted.
Hence, tuning of shell thickness offers one convenient way of adjusting
adhesion properties. A more general theory on the adhesion of vesicles
is presented by Seifert and co-workers [332]. They mainly focused on
shape/shape changes and transitions from free to bound state. In a
later publication shape equations were solved numerically [333]. An ex-
pression for a critical adhesion energy is derived and theoretical results
are compared to the experimental data obtained from Elsner et al.
showing good agreement. Wan and Liu worked out a model for adhe-
sive contact mechanics of a thin-walled capsule to a at substrate within
linear elastic theory [334]. It is demonstrated that an increase of osmotic
pressure can reduce contact area and even provoke detachment of the
capsule from the substrate. Nolte and Fery introduced a method to
align polyelectrolyte capsules on patterned substrates making use of
electrostatic interactions [335]. This approach has been developed fur-
ther to covalently bind the assembled capsules to the substrate [336].
By computational modeling, Alexeev et al. examined the uid driven
76 M.P. Neubauer et al. / Advances in Colloid and Interface Science 207 (2014) 6580
motion of a capsule on a substrate [286,289,337]. They found that be-
sides stiffness and pattern of the substrate the mechanical properties
of the microcapsules play an important role for the tuning of mutual ad-
hesion. Based on these results concepts are introduced to selectively
trap and burst the capsules[338] as well as to sort and guide them in a
predetermined manner[339341]. This opens an application perspec-
tive for, e.g., analytical devices for quality control regarding capsule me-
chanics or for a fractionation device allowing the extraction of capsules
with desired mechanical properties from a given batch. Lastly, for an in-
depth study of shell adhesion, an exhaustive treatment of the topic can
be found in [342].
6. Conclusions
Microcapsule mechanics is a fascinating topic, which has attracted
attention from various scientic communities for many decades. Still,
we are currently witnessing the dawn of a new era: Modern synthetic
approaches like the layer-by-layer technique or other template-
assisted self-assembly methods allow unprecedented control over geo-
metrical parameters of capsules as well as on the composition of wall
and interior. Consequently, mechanical properties like capsule stiffness
in the small deformation range, buckling forces/pressures or burst
forces/fracture strength can be adjusted accurately. This allows not
only tailoring mechanical properties such that sufcient stability to
withstand wear and tear in applications is ensured rather mechanical
properties and instabilities can be taken advantage of for introducing
functionality. The present review focuses on novel possibilities and il-
lustrates them by some selected examples from literature, without
aiming for completeness of this highly dynamic eld. Gaining control
and further understanding of microcapsule mechanics require a truly
interdisciplinary approach. Therefore, the foundations in terms of suit-
able synthesis/assembly are introduced together with theoretical basics
of microcapsules mechanics as well as an overview of experimental
characterization techniques with special emphasis on single microcap-
sule measurements. Thus, we hope to provide an entry point for inter-
ested researchers into this interdisciplinary eld.
References
[1] Jong HGB. Die Koazervation und ihre Bedeutung fr die Biologie. Protoplasma
1932;15:11073.
[2] Bungenbergde Jong HG, Bon-Ner J. Phosphatide auto-complex coacervates as ionic
systems and their relations to the protoplasmic membrane. Protoplasma
1935;24:198218.
[3] Cole KS. Surface forces of the arbacia egg. J Cell Comp Physiol 1932;1:19.
[4] Green BK, Lowell S. Manifold record material. US Patent Ofce, US2730456 A; 1953
[The National Cash Register Company].
[5] Youan BBC, Jackson TL, Dickens L, Hernandez C, Owusu-Ababio G. Protein release
proles and morphology of biodegradable microcapsules containing an oily core.
J Control Release 2001;76:31326.
[6] Kataoka K, Harada A, Nagasaki Y. Block copolymer micelles for drug delivery: design,
characterization and biological signicance. Adv Drug Deliv Rev 2001;47:11331.
[7] Bae Y, Kataoka K. Intelligent polymeric micelles from functional poly(ethylene gly-
col)-poly(amino acid) block copolymers. Adv Drug Deliv Rev 2009;61:76884.
[8] Discher DE, Eisenberg A. Polymer vesicles. Science 2002;297:96773.
[9] Langer R. Drug delivery and targeting. Nature 1998;392:510.
[10] De Geest BG, De Koker S, Sukhorukov GB, Kreft O, Parak WJ, Skirtach AG, et al. Poly-
electrolyte microcapsules for biomedical applications. Soft Matter 2009;5:28291.
[11] Tong WJ, Gao CY. Multilayer microcapsules with tailored structures for bio-related
applications. J Mater Chem 2008;18:3799812.
[12] Madene A, Jacquot M, Scher J, Desobry S. Flavour encapsulation and controlled re-
lease a review. Int J Food Sci Technol 2006;41:121.
[13] Rokka S, Rantamaki P. Protecting probiotic bacteria by microencapsulation: chal-
lenges for industrial applications. Eur Food Res Technol 2010;231:112.
[14] Gharsallaoui A, Roudaut G, Chambin O, Voilley A, Saurel R. Applications of spray-
drying in microencapsulation of food ingredients: an overview. Food Res Int
2007;40:110721.
[15] Arshady R. Microcapsules for food. J Microencapsul 1993;10:41335.
[16] Onwulata CI. Encapsulation of new active ingredients. Annual review of food sci-
ence and technology, vol 3Palo alto: annual reviews, vol. 3; 2012 183202.
[17] Ezhilarasi PN, Karthik P, Chhanwal N, Anandharamakrishnan C. Nanoencapsulation
techniques for food bioactive components: a review. Food Bioprocess Technol
2013;6:62847.
[18] Kandansamy K, Somasundaram PD. Microencapsulation of colors by spray drying
a review. Int J Food Eng 2012;8:17.
[19] Shahidi F, Han XQ. Encapsulation of food ingredients. Crit Rev Food Sci Nutr
1993;33:50147.
[20] Champagne CP, Fustier P. Microencapsulation for the improved delivery of bioac-
tive compounds into foods. Curr Opin Biotechnol 2007;18:18490.
[21] Desai KGH, Park HJ. Recent developments in microencapsulation of food ingredi-
ents. Drying Technol 2005;23:136194.
[22] Gouin S. Microencapsulation: industrial appraisal of existing technologies and
trends. Trends Food Sci Technol 2004;15:33047.
[23] Tsuji K. Microencapsulation of pesticides and their improved handling safety. J
Microencapsul 2001;18:13747.
[24] Salem M, Al-Zayadneh W, Cheruth A. Water Conservation and Management with
Hydrophobic Encapsulation of Sand. Water Resources Management 2010;24:
223746.
[25] Sopena F, Maqueda C, Morillo E. Controlled release formulations of herbicides
based on micro-encapsulation. Cienc Invest Agrar 2009;36:2742.
[26] Hack B, Egger H, Uhlemann J, Henriet M, Wirth W, Vermeer AWP, et al. Advanced
agrochemical formulations through encapsulation strategies? Chem Ing Tech
2012;84:22334.
[27] Moragas M, Garces JG, Petit J-LV. In: Ofce EP, editor. Cosmetic compositions con-
taining chitosan microcapsules., EP1077060A1; 1999 [Primacare S.A].
[28] Ohlberg G, Guder A, Wiedmann J, Pommersheim R. Microcapsules for introducing
substances into cosmeticsIn: Organization WIP, editor. , WO2008043841A3; 2007
[Cavis Microcaps GmbH].
[29] Ammala A. Biodegradable polymers as encapsulation materials for cosmetics and
personal care markets. Int J Cosmet Sci 2013;35:11324.
[30] Nelson G. Application of microencapsulation in textiles. Int J Pharm 2002;242:5562.
[31] Sanchez L, Lacasa E, Carmona M, Rodriguez JF, Sanchez P. Applying an experimental
design to improve the characteristics of microcapsules containing phase change
materials for fabric uses. Ind Eng Chem Res 2008;47:978390.
[32] Teixeira C, Martins IMD, Mata VLG, Barreiro MFF, Rodrigues AE. Characterization
and evaluation of commercial fragrance microcapsules for textile application. J
Text Inst 2011;103:26982.
[33] Akers Jr CE, Sun XJ. Encapsulated pigment for ink-jet ink formulations and methods of
producing same. United States Patent Ofce, US7354962 B1; 2008 [Lexmark Interna-
tional, Inc.Lexington, KY, US].
[34] Park BW, Yoon DY, Kim DS. Recent progress in bio-sensing techniques with encap-
sulated enzymes. Biosens Bioelectron 2010;26:110.
[35] Roitman DB. Microcapsule biosensors and methods of using the same. United
States Patent Ofce, US7312040 B2; 2007 [Agilent Technologies Inc.; USA].
[36] Chaudhary A, McShane MJ, Srivastava R. Glucose response of dissolved-core alginate
microspheres: towards a continuous glucose biosensor. Analyst 2010;135:26208.
[37] Shchukin DG, Grigoriev DO, Mohwald H. Application of smart organic nanocontainers
in feedback active coatings. Soft Matter 2010;6:7205.
[38] Shchukin DG, Mohwald H. Smart nanocontainers as depot media for feedback ac-
tive coatings. Chem Commun 2011;47:87309.
[39] Raj VAA, Velraj R. Review on free cooling of buildings using phase change materials.
Renew Sustain Energy Rev 2010;14:281929.
[40] Waqas A, Din ZU. Phase change material (PCM) storage for free cooling of buildings
a review. Renew Sustain Energy Rev 2013;18:60725.
[41] Boh BS, Bostjan. Microencapsulation technology and its applications in building
construction materials. RMZ-Mater Geoenviron 2008;55:32944.
[42] Ghosh SK. Functional coatings and microencapsulation: a general perspective.
Functional Coatings: Wiley-VCH Verlag GmbH & Co. KGaA; 2006 128.
[43] Luzzi LA. Microencapsulation. J Pharm Sci 1970;59:136776.
[44] Nazzaro F, Orlando P, Fratianni F, Coppola R. Microencapsulation in food science
and biotechnology. Curr Opin Biotechnol 2012;23:1826.
[45] Loscertales IG, Barrero A, Guerrero I, Cortijo R, Marquez M, Ganan-Calvo AM. Micro/
nano encapsulation via electried coaxial liquid jets. Science 2002;295:16958.
[46] Sliwka W. Microencapsulation. Angew Chem Int Ed Engl 1975;14:53950.
[47] Re MI. Microencapsulation by spray drying. Drying Technol 1998;16:1195236.
[48] Utada AS, Lorenceau E, Link DR, Kaplan PD, Stone HA, Weitz DA. Monodisperse double
emulsions generated from a microcapillary device. Science 2005;308:53741.
[49] Chen PW, Erb RM, Studart AR. Designer polymer-based microcapsules made using
microuidics. Langmuir 2012;28:14452.
[50] Hennequin Y, Pannacci N, de Torres CnP, Tetradis-Meris G, Chapuliot S, Bouchaud E,
et al. Synthesizing microcapsules with controlled geometrical and mechanical prop-
erties with microuidic double emulsion technology. Langmuir 2009;25:785761.
[51] Zhang J, Coulston RJ, Jones ST, Geng J, Scherman OA, Abell C. One-step fabrication of
supramolecular microcapsules from microuidic droplets. Science 2012;335:6904.
[52] Zhang H, Tumarkin E, Peerani R, Nie Z, Sullan RMA, Walker GC, et al. Microuidic
production of biopolymer microcapsules with controlled morphology. J Am Chem
Soc 2006;128:1220510.
[53] Chu LY, Utada AS, Shah RK, Kim JW, Weitz DA. Controllable monodisperse multiple
emulsions. Angew Chem Int Edit 2007;46:89704.
[54] Kim JW, Utada AS, Fernandez-Nieves A, Hu ZB, Weitz DA. Fabrication of monodis-
perse gel shells and functional microgels in microuidic devices. Angew Chem Int
Edit 2007;46:181922.
[55] Discher DE, Ahmed F. Polymersomes. Annu Rev Biomed EngPalo Alto: Annual Re-
views, vol. 8; 2006 32341.
[56] Peer D, Karp JM, Hong S, Farokhzad OC, Margalit R, Langer R. Nanocarriers as an
emerging platform for cancer therapy. Nat Nanotechnol 2007;2:75160.
[57] Li MH, Keller P. Stimuli-responsive polymer vesicles. Soft Matter 2009;5:92737.
[58] Meng FH, Zhong ZY, Feijen J. Stimuli-responsive polymersomes for programmed
drug delivery. Biomacromolecules 2009;10:197209.
 M.P. Neubauer et al. / Advances in Colloid and Interface Science 207 (2014) 6580
[59] Onaca O, Enea R, Hughes DW, Meier W. Stimuli-responsive polymersomes as
nanocarriers for drug and gene delivery. Macromol Biosci 2009;9:12939.
[60] Lee JS, Feijen J. Polymersomes for drug delivery: design, formation and characteri-
zation. J Control Release 2012;161:47383.
[61] Velev OD, Furusawa K, Nagayama K. Assembly of latex particles by using emulsion
droplets as templates.1. Microstructured hollow spheres. Langmuir 1996;12:237484.
[62] Dinsmore AD, Hsu MF, Nikolaides MG, Marquez M, Bausch AR, Weitz DA.
Colloidosomes: selectively permeable capsules composed of colloidal particles. Sci-
ence 2002;298:10069.
[63] Rossier-Miranda FJ, Schroen C, Boom RM. Colloidosomes: versatile microcapsules
in perspective. Colloids Surf A Physicochem Eng Asp 2009;343:439.
[64] Arshady R, George MH. Suspension, dispersion, and interfacial polycondensation: a
methodological survey. Polym Eng Sci 1993;33:86576.
[65] Cui JW, Wang YJ, Postma A, Hao JC, Hosta-Rigau L, Caruso F. Monodisperse polymer
capsules: tailoring size, shell thickness, and hydrophobic cargo loading via emul-
sion templating. Adv Funct Mater 2010;20:162531.
[66] Torini L, Argillier JF, Zydowicz N. Interfacial polycondensation encapsulation in
miniemulsion. Macromolecules 2005;38:322536.
[67] Kobaslija M, McQuade DT. Polyurea microcapsules from oil-in-oil emulsions via in-
terfacial polymerization. Macromolecules 2006;39:63715.
[68] Akartuna I, Tervoort E, Studart AR, Gauckler LJ. General route for the assembly of
functional inorganic capsules. Langmuir 2009;25:1241924.
[69] Bohmer MR, Schroeders R, Steenbakkers JAM, de Winter S, Duineveld PA, Lub J,
et al. Preparation of monodisperse polymer particles and capsules by ink-jet print-
ing. Colloids Surf A Physicochem Eng Asp 2006;289:96104.
[70] Dohnal J, Stepanek F. Inkjet fabrication and characterization of calcium alginate mi-
crocapsules. Powder Technol 2010;200:2549.
[71] Arshady R. Microspheres and microcapsules: a survey of manufacturing tech-
niques.2. Coacervation. Polym Eng Sci 1990;30:90514.
[72] Loxley A, Vincent B. Preparation of poly(methylmethacrylate) microcapsules with
liquid cores. J Colloid Interface Sci 1998;208:4962.
[73] Li JA, Stover HDH. Pickering emulsion templated layer-by-layer assembly for mak-
ing microcapsules. Langmuir 2010;26:1555460.
[74] Grigoriev DO, Bukreeva T, Mohwald H, Shchukin DG. New method for fabrication of
loaded micro- and nanocontainers: emulsion encapsulation by polyelectrolyte
layer-by-layer deposition on the liquid core. Langmuir 2008;24:9991004.
[75] Decher G. Fuzzy nanoassemblies: toward layered polymeric multicomposites. Sci-
ence 1997;277:12327.
[76] Sukhorukov GB, Donath E, Davis S, Lichtenfeld H, Caruso F, Popov VI, et al. Stepwise
polyelectrolyte assembly on particle surfaces: a novel approach to colloid design.
Polym Adv Technol 1998;9:75967.
[77] del Mercato LL, Rivera-Gil P, Abbasi AZ, Ochs M, Ganas C, Zins I, et al. LbL multilayer
capsules: recent progress and future outlook for their use in life sciences. Nanoscale
2010;2:45867.
[78] Skirtach AG, Yashchenok AM, Mohwald H. Encapsulation, release and applications
of LbL polyelectrolyte multilayer capsules. Chem Commun 2011;47:1273646.
[79] Caruso F, Caruso RA, Mohwald H. Nanoengineering of inorganic and hybrid hollow
spheres by colloidal templating. Science 1998;282:11114.
[80] Caruso F, Spasova M, Saigueirino-Maceira V, Liz-Marzan LM. Multilayer assemblies
of silica-encapsulated gold nanoparticles on decomposable colloid templates. Adv
Mater 2001;13:1090.
[81] Mller R, Daehne L, Fery A. Hollow polyelectrolyte multilayer tubes: mechanical
properties and shape changes. J Phys Chem B 2007;111:854753.
[82] Peyratout CS, Dhne L. Tailor-made polyelectrolyte microcapsules: from multi-
layers to smart containers. Angew Chem Int Ed 2004;43:376283.
[83] Sukhorukov GB, Mohwald H. Multifunctional cargo systems for biotechnology.
Trends Biotechnol 2007;25:938.
[84] Poncelet D, Neufeld RJ. Shear breakage of nylon membrane microcapsules in a tur-
bine reactor. Biotechnol Bioeng 1989;33:95103.
[85] Drochon A. Rheology of dilute suspensions of red blood cells: experimental and
theoretical approaches. Eur Phys J Appl Phys 2003;22:15562.
[86] Drochon A, Barthesbiesel D, Lacombe C, Lelievre JC. Determination of the red blood
cell apparent membrane elastic modulus from viscometric measurements. J
Biomech Eng Trans ASME 1990;112:2419.
[87] Barthesbiesel D. Motion of a spherical microcapsule freely suspended in a linear
shear-ow. J Fluid Mech 1980;100:83153.
[88] Barthesbiesel D, Rallison JM. The time-dependent deformation of a capsule freely
suspended in a linear shear-ow. J Fluid Mech 1981;113:25167.
[89] Barthesbiesel D, Sgaier H. Role of membrane viscosity in the orientation and
deformation of a spherical capsule suspended in shear-ow. J Fluid Mech
1985;160:11935.
[90] Ramanujan S, Pozrikidis C. Deformation of liquid capsules enclosed by elastic mem-
branes in simple shear ow: large deformations and the effect of uid viscosities. J
Fluid Mech 1998;361:11743.
[91] Bredimas M, Veyssie M, Barthesbiesel D, Chhim V. Model suspension of spherical cap-
sulesphysical and rheological properties. J Colloid Interface Sci 1983;93:51320.
[92] Danker G, Biben T, Podgorski T, Verdier C, Misbah C. Dynamics and rheology of a
dilute suspension of vesicles: higher-order theory. Phys Rev E 2007;76:10.
[93] Danker G, Misbah C. Rheology of a dilute suspension of vesicles. Phys Rev Lett
2007;98:4.
[94] Danker G, Verdier C, Misbah C. Rheology and dynamics of vesicle suspension in com-
parison with droplet emulsion. J Non-Newtonian Fluid Mech 2008;152:15667.
[95] Farutin A, Misbah C. Rheology of vesicle suspensions under combined steady and
oscillating shear ows. J Fluid Mech 2012;700:36281.
[96] Ghigliotti G, Biben T, Misbah C. Rheology of a dilute two-dimensional suspension of
vesicles. J Fluid Mech 2010;653:489518.
77
[97] Bagchi P, Kalluri RM. Dynamic rheology of a dilute suspension of elastic capsules: ef-
fect of capsule tank-treading, swinging and tumbling. J Fluid Mech 2011;669:
498526.
[98] Bagchi P, Kalluri RM. Rheology of a dilute suspension of liquid-lled elastic cap-
sules. Phys Rev E 2010;81:11.
[99] Gao C, Donath E, Moya S, Dudnik V, Mohwald H. Elasticity of hollow polyelec-
trolyte capsules prepared by the layer-by-layer technique. Eur Phys J E 2001;5:
217.
[100] Gao CY, Leporatti S, Moya S, Donath E, Mohwald H. Stability and mechanical
properties of polyelectrolyte capsules obtained by stepwise assembly of
poly(styrenesulfonate sodium salt) and poly(diallyldimethyl ammonium) chloride
onto melamine resin particles. Langmuir 2001;17:34915.
[101] Datta SS, Shum HC, Weitz DA. Controlled buckling and crumpling of nanoparticle-
coated droplets. Langmuir 2010;26:186126.
[102] Zhang Z, Saunders R, Thomas CR. Mechanical strength of single microcapsules
determined by a novel micromanipulation technique. J Microencapsul
1999;16:11724.
[103] Hu JF, Chen HQ, Zhang ZB. Mechanical properties of melamine formaldehyde mi-
crocapsules for self-healing materials. Mater Chem Phys 2009;118:6370.
[104] Keller MW, Sottos NR. Mechanical properties of microcapsules used in a self-
healing polymer. Exp Mech 2006;46:72533.
[105] Rachik M, Barthes-Biesel D, Carin M, Edwards-Levy F. Identication of the elastic
properties of an articial capsule membrane with the compression test: effect of
thickness. J Colloid Interface Sci 2006;301:21726.
[106] Mercade-Prieto R, Allen R, Zhang ZB, York D, Preece JA, Goodwin TE. Failure of elastic-
plastic core-shell microcapsules under compression. Aiche J 2012;58:267481.
[107] Mercade-Prieto R, Nguyen B, Allen R, York D, Preece JA, Goodwin TE, et al. Determi-
nation of the elastic properties of single microcapsules using micromanipulation
and nite element modeling. Chem Eng Sci 2011;66:20429.
[108] Carin M, Barthes-Biesel D, Edwards-Levy F, Postel C, Andrei DC. Compression of
biocompatible liquid-lled HSA-alginate capsules: determination of the membrane
mechanical properties. Biotechnol Bioeng 2003;82:20712.
[109] Fery A, Weinkamer R. Mechanical properties of micro- and nanocapsules: single-
capsule measurements. Polymer 2007;48:722135.
[110] Lulevich VV, Radtchenko IL, Sukhorukov GB, Vinogradova OI. Deformation proper-
ties of nonadhesive polyelectrolyte microcapsules studied with the atomic force
microscope. J Phys Chem B 2003;107:273540.
[111] Lulevich VV, Andrienko D, Vinogradova OI. Elasticity of polyelectrolyte multilayer
microcapsules. J Chem Phys 2004;120:38226.
[112] Lebedeva OV, Kim BS, Vinogradova OI. Mechanical properties of polyelectrolyte-
lled multilayer microcapsules studied by atomic force and confocal microscopy.
Langmuir 2004;20:1068590.
[113] Dubreuil F, Elsner N, Fery A. Elastic properties of polyelectrolyte capsules studied
by atomic-force microscopy and RICM. Eur Phys J E 2003;12:21521.
[114] Elsner N, Dubreuil F, Fery A. Tuning of microcapsule adhesion by varying the
capsule-wall thickness. Phys Rev E 2004;69:6.
[115] Fery A, Dubreuil F, Mohwald H. Mechanics of articial microcapsules. New J Phys
2004;6:13.
[116] Liang XM, Mao GZ, Ng KYS. Mechanical properties and stability measurement of
cholesterol-containing liposome on mica by atomic force microscopy. J Colloid In-
terface Sci 2004;278:5362.
[117] Pretzl M, Neubauer M, Tekaat M, Kunert C, Kuttner C, Leon G, et al. Formation and
mechanical characterization of aminoplast core/shell microcapsules. ACS Appl
Mater Interfaces 2012;4:29408.
[118] Palankar R, Pinchasik BE, Schmidt S, De Geest BG, Fery A, Mohwald H, et al. Me-
chanical strength and intracellular uptake of CaCO3-templated LbL capsules com-
posed of biodegradable polyelectrolytes: the inuence of the number of layers. J
Mater Chem B 2013;1:117581.
[119] Heuvingh J, Zappa M, Fery A. Salt softening of polyelectrolyte multilayer capsules.
Langmuir 2005;21:316571.
[120] Delorme N, Fery A. Direct method to study membrane rigidity of small vesicles
based on atomic force microscope force spectroscopy. Phys Rev E 2006;74:3.
[121] Chen Q, Schonherr H, Vancso GJ. Mechanical properties of block copolymer vesicle
membranes by atomic force microscopy. Soft Matter 2009;5:494450.
[122] Zoldesi CI, Ivanovska IL, Quilliet C, Wuite GJL, Imhof A. Elastic properties of hollow
colloidal particles. Phys Rev E 2008;78:8.
[123] Zhang L, D'Acunzi M, Kappl M, Auernhammer GK, Vollmer D, van Kats CM, et al. Hol-
low silica spheres: synthesis and mechanical properties. Langmuir 2009;25:27117.
[124] Cuellar JL, Meinhoevel F, Hoehne M, Donath E. Size and mechanical stability of
norovirus capsids depend on pH: a nanoindentation study. J Gen Virol
2010;91:244956.
[125] Roos WH, Bruinsma R, Wuite GJL. Physical virology. Nat Phys 2010;6:73343.
[126] Jaskiewicz K, Makowski M, Kappl M, Landfester K, Kroeger A. Mechanical proper-
ties of poly(dimethylsiloxane)-block-poly(2-methyloxazoline) polymersomes
probed by atomic force microscopy. Langmuir 2012;28:1262936.
[127] Sboros V, Glynos E, Pye SD, Moran CM, Butler M, Ross JA, et al. Nanomechanical
probing of microbubbles using the atomic force microscope. Ultrasonics 2007;46:
34954.
[128] Glynos E, Koutsos V, McDicken WN, Moran CM, Pye SD, Ross JA, et al.
Nanomechanics of biocompatible hollow thin-shell polymer microspheres. Lang-
muir 2009;25:751422.
[129] Grant CA, McKendry JE, Evans SD. Temperature dependent stiffness and visco-
elastic behaviour of lipid coated microbubbles using atomic force microscopy.
Soft Matter 2012;8:13216.
[130] Santos EB, Morris JK, Glynos E, Sboros V, Koutsos V. Nanomechanical properties of
phospholipid microbubbles. Langmuir 2012;28:575360.
78 M.P. Neubauer et al. / Advances in Colloid and Interface Science 207 (2014) 6580
[131] Chen CC, Wu SY, Finan JD, Morrison B, Konofagou EE. An experimental study on the
stiffness of size-isolated microbubbles using atomic force microscopy. IEEE Trans
Ultrason Ferroelectr Freq Control 2013;60:52434.
[132] Chang KS, Olbricht WL. Experimental studies of the deformation and breakup of a
synthetic capsule in steady and unsteady simple shear-ow. J Fluid Mech
1993;250:60933.
[133] Walter A, Rehage H, Leonhard H. Shear induced deformation of microcapsules:
shape oscillations and membrane folding. Colloids Surf A Physicochem Eng Asp
2001;183185:12332.
[134] Rehage H, Husmann M, Walter A. From two-dimensional model networks to mi-
crocapsules. Rheol Acta 2002;41:292306.
[135] Walter A, Rehage H, Leonhard H. Shear-induced deformations of polyamide micro-
capsules. Colloid Polym Sci 2000;278:16975.
[136] Koleva I, Rehage H. Deformation and orientation dynamics of polysiloxane micro-
capsules in linear shear ow. Soft Matter 2012;8:368193.
[137] Degen P, Leick S, Rehage H. Mechanical stability of ionotropic alginate beads. Z Phys
Chemie-Int J Res Phys Chem Chem Phys 2009;223:107990.
[138] Pieper G, Rehage H, Barthes-Biesel D. Deformation of a capsule in a spinning drop
apparatus. J Colloid Interface Sci 1998;202:293300.
[139] Leick S, Kott M, Degen P, Henning S, Pasler T, Suter D, et al. Mechanical properties of
liquid-lled shellac composite capsules. Phys Chem Chem Phys 2011;13:276573.
[140] Husmann M, Rehage H, Dhenin E, Barthes-Biesel D. Deformation and bursting of
nonspherical polysiloxane microcapsules in a spinning-drop apparatus. J Colloid
Interface Sci 2005;282:10919.
[141] Leick S, Kemper A, Rehage H. Alginate/poly-L-lysine capsules: mechanical proper-
ties and drug release characteristics. Soft Matter 2011;7:668494.
[142] Leick S, Henning S, Degen P, Suter D, Rehage H. Deformation of liquid-lled calcium
alginate capsules in a spinning drop apparatus. Phys Chem Chem Phys
2010;12:29508.
[143] Lac E, Barthes-Biesel D, Pelekasis NA, Tsamopoulos J. Spherical capsules in three-
dimensional unbounded Stokes ows: effect of the membrane constitutive law
and onset of buckling. J Fluid Mech 2004;516:30334.
[144] Barthes-Biesel D. Capsule motion in ow: deformation and membrane buckling. C
R Phys 2009;10:76474.
[145] Finken R, Kessler S, Seifert U. Micro-capsules in shear ow. J Phys: Condens Matter
2011;23:184113.
[146] Barthes-Biesel D. Modeling the motion of capsules in ow. Curr Opin Colloid Inter-
face Sci 2011;16:312.
[147] Kessler S, Finken R, Seifert U. Swinging and tumbling of elastic capsules in shear
ow. J Fluid Mech 2008;605:20726.
[148] Lac E, Barthes-Biesel D. Deformation of a capsule in simple shear ow: effect of
membrane prestress. Phys Fluids 2005;17:8.
[149] Viades-Trejo J, Gracia-Fadrique J. Spinning drop method from YoungLaplace to
Vonnegut. Colloids Surf A: Physicochem Eng Aspect 2007;302:54952.
[150] Tomaiuolo G, Simeone M, Martinelli V, Rotoli B, Guido S. Red blood cell deforma-
tion in microconned ow. Soft Matter 2009;5:373640.
[151] Lefebvre Y, Leclerc E, Barthes-Biesel D, Walter J, Edwards-Levy F. Flow of articial
microcapsules in microuidic channels: a method for determining the elastic prop-
erties of the membrane. Phys Fluids 2008;20:10.
[152] She SP, Xu CX, Yin XF, Tong WJ, Gao CY. Shape deformation and recovery of multi-
layer microcapsules after being squeezed through a microchannel. Langmuir
2012;28:50106.
[153] Leclerc E, Kinoshita H, Fujii T, Barthes-Biesel D. Transient ow of microcapsules
through convergentdivergent microchannels. Microuid Nanouid
2012;12:76170.
[154] Chu TX, Salsac AV, Leclerc E, Barthes-Biesel D, Wurtz H, Edwards-Levy F. Compar-
ison between measurements of elasticity and free amino group content of ovalbu-
min microcapsule membranes: discrimination of the cross-linking degree. J Colloid
Interface Sci 2011;355:818.
[155] Coupier G, Farutin A, Minetti C, Podgorski T, Misbah C. Shape diagram of vesicles in
Poiseuille ow. Phys Rev Lett 2012;108:5.
[156] Farutin A, Misbah C. Analytical and numerical study of three main migration laws
for vesicles under ow. Phys Rev Lett 2013;110:5.
[157] Hu XQ, Salsac AV, Barthes-Biesel D. Flow of a spherical capsule in a pore with cir-
cular or square cross-section. J Fluid Mech 2012;705:17694.
[158] Kuriakose S, Dimitrakopoulos P. Motion of an elastic capsule in a square
microuidic channel. Phys Rev E 2011;84:22.
[159] Li H, Ma G. Modeling performance of a two-dimensional capsule in a microchannel
ow: long-term lateral migration. Phys Rev E 2010;82:14.
[160] Ma G, Hua JS, Li H. Numerical modeling of the behavior of an elastic capsule in a
microchannel ow: the initial motion. Phys Rev E 2009;79:17.
[161] Queguiner C, BarthesBiesel D. Axisymmetric motion of capsules through cylindrical
channels. J Fluid Mech 1997;348:34976.
[162] Lefebvre Y, Barthes-Biesel D. Motion of a capsule in a cylindrical tube: effect of
membrane pre-stress. J Fluid Mech 2007;589:15781.
[163] Mitchison JM, Swann MM. The mechanical properties of the cell surface.1. The cell
elastimeter. J Exp Biol 1954;31:443.
[164] Rand RP, Burton AC. Mechanical properties of red cell membrane. I. membrane
stiffness + intracellular pressure. Biophys J 1964;4:115.
[165] Hochmuth RM. Micropipette aspiration of living cells. J Biomech 2000;33:1522.
[166] Kim DH, Wong PK, Park J, Levchenko A, Sun Y. Microengineered platforms for cell
mechanobiology. Annu Rev Biomed Eng 2009;11:20333.
[167] Chien S, Sung KLP, Skalak R, Usami S. Theoretical and experimental studies on vis-
coelastic properties erythrocyte-membrane. Biophys J 1978;24:46387.
[168] Evans E, Yeung A. Apparent viscosity and cortical tension of blood granulocytes de-
termined by micropipet aspiration. Biophys J 1989;56:15160.
[169] Shao JY, Hochmuth RM. Micropipette suction for measuring piconewton forces
of adhesion and tether formation from neutrophil membranes. Biophys J
1996;71:2892901.
[170] Dieluweit S, Csiszar A, Rubner W, Fleischhauer J, Houben S, Merkel R. Mechanical
properties of bare and protein-coated giant unilamellar phospholipid vesicles. a
comparative study of micropipet aspiration and atomic force microscopy. Lang-
muir 2010;26:110419.
[171] Ratanabanangkoon P, Gropper M, Merkel R, Sackmann E, Gast AP. Mechanics of
streptavidin-coated giant lipid bilayer vesicles: a micropipet study. Langmuir
2003;19:105462.
[172] Rawicz W, Olbrich KC, McIntosh T, Needham D, Evans E. Effect of chain length and
unsaturation on elasticity of lipid bilayers. Biophys J 2000;79:32839.
[173] Mabrouk E, Cuvelier D, Pontani LL, Xu B, Levy D, Keller P, et al. Formation and ma-
terial properties of giant liquid crystal polymersomes. Soft Matter 2009;5:18708.
[174] Evans EA. New membrane concept applied to analysis of uid shear-deformed and
micropipet-deformed red blood-cells. Biophys J 1973;13:94154.
[175] Skalak R, Tozeren A, Zarda RP, Chien S. Strain energy function of red blood-cell
membranes. Biophys J 1973;13:24580.
[176] Sohail T, Tang T, Nadler B. Micropipette aspiration of an inated uid-lled spher-
ical membrane. Z Angew Math Phys 2012;63:73757.
[177] Heinrich V, Ounkomol C. Force versus axial deection of pipette-aspirated closed
membranes. Biophys J 2007;93:36372.
[178] Baaijens FPT, Trickey WR, Laursen TA, Guilak F. Large deformation nite element
analysis of micropipette aspiration to determine the mechanical properties of the
chondrocyte. Ann Biomed Eng 2005;33:494501.
[179] Theret DP, Levesque MJ, Sato M, Nerem RM, Wheeler LT. The application of a ho-
mogeneous half-space model in the analysis of endothelial-cell micropipette mea-
surements. J Biomech Eng Trans ASME 1988;110:1909.
[180] Discher DE, Boal DH, Boey SK. Simulations of the erythrocyte cytoskeleton at large
deformation. II. Micropipette aspiration. Biophys J 1998;75:158497.
[181] Ashkin A. Acceleration and trapping of particles by radiation pressure. Phys Rev
Lett 1970;24:156.
[182] Svoboda K, Block SM. Biological applications of optical forces. Annu Rev Biophys
Biomol Struct 1994;23:24785.
[183] Neuman KC, Nagy A. Single-molecule force spectroscopy: optical tweezers, mag-
netic tweezers and atomic force microscopy. Nat Methods 2008;5:491505.
[184] Noy A. Handbook of molecular force spectroscopy. New York: Springer; 2008.
[185] Zhang H, Liu KK. Optical tweezers for single cells. J R Soc Interface 2008;5:67190.
[186] Henon S, Lenormand G, Richert A, Gallet F. A new determination of the shear mod-
ulus of the human erythrocyte membrane using optical tweezers. Biophys J
1999;76:114551.
[187] Sleep J, Wilson D, Simmons R, Gratzer W. Elasticity of the red cell membrane and
its relation to hemolytic disorders: an optical tweezers study. Biophys J
1999;77:308595.
[188] Dao M, Lim CT, Suresh S. Mechanics of the human red blood cell deformed by op-
tical tweezers. J Mech Phys Solids 2003;51:225980.
[189] Titushkin I, Cho M. Distinct membrane mechanical properties of human mesen-
chymal stem cells determined using laser optical tweezers. Biophys J
2006;90:258291.
[190] Frases S, Pontes B, Nimrichter L, Rodrigues ML, Viana NB, Casadevall A. The
elastic properties of the Cryptococcus neoformans capsule. Biophys J 2009;97:
93745.
[191] Viana NB, Rocha MS, Mesquita ON, Mazolli A, Neto PAM, Nussenzveig HM. Towards
absolute calibration of optical tweezers. Phys Rev E 2007;75:14.
[192] Dutra RS, Viana NB, Neto PAM, Nussenzveig HM. Absolute calibration of optical
tweezers including aberrations. Appl Phys Lett 2012;100:3.
[193] Guck J, Ananthakrishnan R, Mahmood H, Moon TJ, Cunningham CC, Kas J. The op-
tical stretcher: a novel laser tool to micromanipulate cells. Biophys J
2001;81:76784.
[194] Bareil PB, Sheng Y, Chen YQ, Chiou A. Calculation of spherical red blood cell defor-
mation in a dual-beam optical stretcher. Opt Express 2007;15:1602934.
[195] Ekpenyong AE, Posey CL, Chaput JL, Burkart AK, Marquardt MM, Smith TJ, et al. De-
termination of cell elasticity through hybrid ray optics and continuum mechanics
modeling of cell deformation in the optical stretcher. Appl Optics
2009;48:634454.
[196] Skelton SE, Sergides M, Memoli G, Marago OM, Jones PH. Trapping and deformation
of microbubbles in a dual-beam bre-optic trap. J Opt 2012;14:10.
[197] Bausch AR, Ziemann F, Boulbitch AA, Jacobson K, Sackmann E. Local measurements
of viscoelastic parameters of adherent cell surfaces by magnetic bead
microrheometry. Biophys J 1998;75:203849.
[198] Bausch AR, Moller W, Sackmann E. Measurement of local viscoelasticity and forces
in living cells by magnetic tweezers. Biophys J 1999;76:5739.
[199] Kamgoue A, Ohayon J, Tracqui P. Estimation of cell young's modulus of adherent
cells probed by optical and magnetic tweezers: inuence of cell thickness and
bead immersion. J Biomech Eng Trans ASME 2007;129:52330.
[200] Lim CT, Dao M, Suresh S, Sow CH, Chew KT. Large deformation of living cells using
laser traps. Acta Mater 2004;52:183745.
[201] Ramm E, Wall WA. Shell structuresa sensitive interrelation between physics and
numerics. Int J Numer Methods Eng 2004;60:381427.
[202] Ventsel E, Krauthammer T. Thin plates and shells. New York: Marcel Dekker; 2001.
[203] Reissner E. Stresses and small displacements of shallow spherical shells.1. J Math
Phys 1946;25:805.
[204] Reissner E. Stresses and small displacements of shallow spherical shells.2. J Math
Phys 1946;25:279300.
[205] Reissner E. The edge effect in symmetric bending of shallow shells of revolution.
Commun Pur Appl Math 1959;12:38598.
 M.P. Neubauer et al. / Advances in Colloid and Interface Science 207 (2014) 6580
[206] Reissner E. Symmetric bending of shallow shells of revolution. J Math Mech
1958;7:12140.
[207] Reissner E, Wan FYM. Rotationally symmetric stress and strain in shells of revolu-
tion. Stud Appl Math 1969;48:1.
[208] Ferri JK, Carl P, Gorevski N, Russell TP, Wang Q, Boker A, et al. Separating mem-
brane and surface tension contributions in Pickering droplet deformation. Soft
Matter 2008;4:225966.
[209] Tan SY, Tabor RF, Ong L, Stevens GW, Dagastine RR. Nano-mechanical properties of
clay-armoured emulsion droplets. Soft Matter 2012;8:311221.
[210] Pogorelov AV, Babenko VI. Geometric methods in the theory of stability of thin
shells (review). Int Appl Mech 1992;28:117.
[211] Liu KK, Williams DR, Briscoe BJ. Compressive deformation of a single microcapsule.
Phys Rev E 1996;54:667380.
[212] Pujara P, Lardner TJ. Deformations of elastic membranes effect of different con-
stitutive relations. Z Angew Math Phys 1978;29:31527.
[213] Dodson WR, Dimitrakopoulos P. Dynamics of strain-hardening and strain-softening
capsules in strong planar extensional ows via an interfacial spectral boundary el-
ement algorithm for elastic membranes. J Fluid Mech 2009;641:26396.
[214] Dimitrakopoulos P. Analysis of the variation in the determination of the shear mod-
ulus of the erythrocyte membrane: effects of the constitutive law and membrane
modeling. Phys Rev E 2012;85:041917.
[215] Arnoldi M, Fritz M, Bauerlein E, Radmacher M, Sackmann E, Boulbitch A. Bacterial
turgor pressure can be measured by atomic force microscopy. Phys Rev E
2000;62:103444.
[216] Boulbitch A. Deformation of the envelope of a spherical Gram-negative bacterium dur-
ing the atomic force microscopic measurements. J Electron Microsc 2000;49:45962.
[217] Wan KT, Chan V, Dillard DA. Constitutive equation for elastic indentation of a thin-
walled bio-mimetic microcapsule by an atomic force microscope tip. Colloids Surf
B: Biointerfaces 2003;27:2418.
[218] Yao X, Walter J, Burke S, Stewart S, Jericho MH, Pink D, et al. Atomic force micros-
copy and theoretical considerations of surface properties and turgor pressures of
bacteria. Colloids Surf B: Biointerfaces 2002;23:21330.
[219] Zhongcan OY, Helfrich W. Bending energy of vesicle membranes general expres-
sions for the 1st, 2nd, and 3rd variation of the shape energy and applications to
spheres and cylinders. Phys Rev A 1989;39:52808.
[220] Landau LD, Lifschitz EM. Course of theoretical physics. 3rd ed. Oxford: Butterworth-
Heinemann; 1997.
[221] Pogorelov AV. Bending of surface and stability of capsules: American mathematical
society; 1988.
[222] Vliegenthart GA, Gompper G. Compression, crumpling and collapse of spherical
shells and capsules. New J Phys 2011;13:24.
[223] Landau LD, Lifschitz EM. Theory of elasticity. Oxford: Butterworth-Heinemann;
1986.
[224] Pauchard L, Pomeau Y, Rica S. Deformation of elastic shells. C R Acad Sci Ser II B
1997;324:4118.
[225] Vaziri A, Mahadevan L. Localized and extended deformations of elastic shells. Proc
Natl Acad Sci U S A 2008;105:79138.
[226] Yildirim B, Yukseler RF. Effect of compressibility on nonlinear buckling of simply
supported polyurethane spherical shells subjected to an apical load. J Elastomers
Plast 2011;43:16787.
[227] Pauchard L, Rica S. Contact and compression of elastic spherical shells: the physics
of a ping-pong ball. Philos Mag B Phys Condens Matter Stat Med Electron Opt
Magn Prop 1998;78:22533.
[228] Parker KH, Winlove CP. The deformation of spherical vesicles with permeable,
constant-area membranes: application to the red blood cell. Biophys J
1999;77:3096107.
[229] Shorter R, Smith JD, Coveney VA, Buseld JJC. Axial compression of hollow elastic
spheres. J Mech Mater Struct 2010;5:693705.
[230] Knoche S, Kierfeld J. Buckling of spherical capsules. Phys Rev E 2011;84:13.
[231] Datta SS, Kim SH, Paulose J, Abbaspourrad A, Nelson DR, Weitz DA. Delayed buck-
ling and guided folding of inhomogeneous capsules. Phys Rev Lett 2012;109:5.
[232] Komura S, Tamura K, Kato T. Buckling of spherical shells adhering onto a rigid sub-
strate. Eur Phys J E 2005;18:34358.
[233] Bauer L, Reiss EL, Keller HB. Axisymmetric buckling of hollow spheres and hemi-
spheres. Commun Pur Appl Math 1970;23:529.
[234] Reboux S, Richardson G, Jensen OE. An asymptotic analysis of the buckling of a
highly shear-resistant vesicle. Eur J Appl Math 2009;20:479518.
[235] Helfer E, Harlepp S, Bourdieu L, Robert J, MacKintosh FC, Chatenay D. Buckling
of actin-coated membranes under application of a local force. Phys Rev Lett
2001;87:4.
[236] Quilliet C. Depressions at the surface of an elastic spherical shell submitted to ex-
ternal pressure. Phys Rev E 2006;74:6.
[237] Siber A. Buckling transition in icosahedral shells subjected to volume conservation
constraint and pressure: relations to virus maturation. Phys Rev E 2006;73:10.
[238] Preston SP, Jensen OE, Richardson G. Buckling of an axisymmetric vesicle
under compression: the effects of resistance to shear. Q J Mech Appl Math
2008;61:124.
[239] Siber A, Podgornik R. Stability of elastic icosadeltahedral shells under uniform
external pressure: application to viruses under osmotic pressure. Phys Rev E
2009;79:5.
[240] Quilliet C, Zoldesi C, Riera C, van Blaaderen A, Imhof A. Anisotropic colloids through
non-trivial buckling. Eur Phys J E 2008;27:1320.
[241] Quemeneur F, Quilliet C, Faivre M, Viallat A, Pepin-Donat B. Gel phase vesicles
buckle into specic shapes. Phys Rev Lett 2012;108:5.
[242] Quilliet C. Numerical deation of beach balls with various Poisson's ratios: from
sphere to bowl's shape. Eur Phys J E 2012;35:9.
79
[243] Vella D, Ajdari A, Vaziri A, Boudaoud A. Wrinkling of pressurized elastic shells. Phys
Rev Lett 2011;107:5.
[244] Vella D, Ajdari A, Vaziri A, Boudaoud A. The indentation of pressurized elastic
shells: from polymeric capsules to yeast cells. J R Soc Interface 2012;9:44855.
[245] Landau LD, Lifschitz EM. Elastizittstheorie. Berlin: Akademie; 1991.
[246] Taber LA. Large deection of a uid-lled spherical-shell under a point load. J Appl
Mech Trans ASME 1982;49:1218.
[247] Sun G, Zhang Z. Mechanical properties of melamine-formaldehyde microcapsules. J
Microencapsul 2001;18:593602.
[248] Gompper G, Kroll DM. Network models of uid, hexatic and polymerized mem-
branes. J Phys Condens Matter 1997;9:8795834.
[249] Evans E, Rawicz W. Entropy-driven tension and bending elasticity in condensed-
uid membranes. Phys Rev Lett 1990;64:20947.
[250] Evans EA. Bending resistance and chemically-induced moments in membrane bi-
layers. Biophys J 1974;14:92331.
[251] Gompper G, Kroll DM. Statistical mechanics of membranes: freezing, undulations,
and topology uctuations. J Phys Condens Matter 2000;12:A2937.
[252] Helfer E, Harlepp S, Bourdieu L, Robert J, MacKintosh FC, Chatenay D. Viscoelastic
properties of actin-coated membranes. Phys Rev E 2001;63 [art. no.-021904.].
[253] Kwak S, Pozrikidis C. Effect of membrane bending stiffness on the axisymmetric de-
formation of capsules in uniaxial extensional ow. Phys Fluids 2001;13:123442.
[254] Pozrikidis C. Effect of membrane bending stiffness on the deformation of capsules
in simple shear ow. J Fluid Mech 2001;440:26991.
[255] Bermudez H, Hammer DA, Discher DE. Effect of bilayer thickness on membrane
bending rigidity. Langmuir 2004;20:5403.
[256] Barthes-Biesel D, Diaz A, Dhenin E. Effect of constitutive laws for two-dimensional
membranes on ow-induced capsule deformation. J Fluid Mech 2002;460:21122.
[257] Simmonds JG, Wan FYM. An asymptotic analysis of the three-dimensional displace-
ments and stresses in a spherical shell under inward radially opposed concentrated
surface loads. Int J Solids Struct 2001;38:686987.
[258] Tu ZC, Ge LQ, Li JB, Ou-Yang ZC. Elasticity of polymer vesicles by osmotic pressure:
an intermediate theory between uid membranes and solid shells. Phys Rev E
2005;72:7.
[259] Zhou H, Pozrikidis C. Deformation of liquid capsules with incompressible interfaces
in simple shear-ow. J Fluid Mech 1995;283:175200.
[260] Delorme N, Dubois M, Garnier S, Laschewsky A, Weinkamer R, Zemb T, et al. Sur-
face immobilization and mechanical properties of catanionic hollow faceted poly-
hedrons. J Phys Chem B 2006;110:17528.
[261] Lazarus A, Florijn HCB, Reis PM. Geometry-induced rigidity in nonspherical pres-
surized elastic shells. Phys Rev Lett 2012;109:5.
[262] Vella D, Ajdari A, Vaziri A, Boudaoud A. Indentation of ellipsoidal and cylindrical
elastic shells. Phys Rev Lett 2012;109:5.
[263] Nguyen TT, Bruinsma RF, Gelbart WM. Elasticity theory and shape transitions of
viral shells. Phys Rev E 2005;72:19.
[264] Mueller R, Daehne L, Fery A. Preparation and mechanical characterization of arti-
cial hollow tubes. Polymer 2007;48:25205.
[265] de Pablo PJ, Schaap IAT, MacKintosh FC, Schmidt CF. Deformation and collapse of
microtubules on the nanometer scale. Phys Rev Lett 2003;91:4.
[266] Shchepelina O, Kozlovskaya V, Kharlampieva E, Mao WB, Alexeev A, Tsukruk VV. An-
isotropic micro- and nano-capsules. Macromol Rapid Commun 2010;31:20416.
[267] Kozlovskaya V, Wang Y, Higgins W, Chen J, Chen Y, Kharlampieva E. pH-triggered
shape response of cubical ultrathin hydrogel capsules. Soft Matter 2012;8:982839.
[268] Zienkiewicz OC, Taylor RL. The nite element method for solid and structural me-
chanics. Oxford: Elsevier Butterworth-Heinemann; 2005.
[269] Zienkiewicz OC, Taylor RL, Zhu JZ. The nite element method: its basis and funda-
mentals. Oxford: Elsevier Butterworth-Heinemann; 2005.
[270] Reddy JN. An introduction to the nite element method. New York: McGraw-Hill
Higher Education; 2006.
[271] Lim TJ, Smith B, McDowell DL. Behavior of a random hollow sphere metal foam.
Acta Mater 2002;50:286779.
[272] MacMeccan RM, Clausen JR, Neitzel GP, Aidun CK. Simulating deformable particle
suspensions using a coupled lattice-Boltzmann and nite-element method. J
Fluid Mech 2009;618:1339.
[273] Kruger T, Varnik F, Raabe D. Efcient and accurate simulations of deformable par-
ticles immersed in a uid using a combined immersed boundary lattice Boltzmann
nite element method. Comput Math Appl 2010;61:3485505.
[274] Walter J, Salsac AV, Barthes-Biesel D, Le Tallec P. Coupling of nite element and
boundary integral methods for a capsule in a Stokes ow. Int J Numer Methods
Eng 2010;83:82950.
[275] Gibbons MM, Klug WS. Nonlinear nite-element analysis of nanoindentation of
viral capsids. Phys Rev E 2007;75:11.
[276] Ahadi A, Colomo J, Evilevitch A. Three-dimensional simulation of nanoindenta-
tion response of viral capsids. shape and size effects. J Phys Chem B 2009;113:
33708.
[277] Ahadi A, Johansson D, Evilevitch A. Modeling and simulation of the mechanical re-
sponse from nanoindentation test of DNA-lled viral capsids. J Biol Phys
2013;39:18399.
[278] Roos WH, Gibbons MM, Arkhipov A, Uetrecht C, Watts NR, Wingeld PT, et al.
Squeezing protein shells: how continuum elastic models, molecular dynamics sim-
ulations, and experiments coalesce at the nanoscale. Biophys J 2010;99:117581.
[279] Lidmar J, Mirny L, Nelson DR. Virus shapes and buckling transitions in spherical
shells. Phys Rev E 2003;68:10.
[280] Vliegenthart GA, Gompper G. Mechanical deformation of spherical viruses with
icosahedral symmetry. Biophys J 2006;91:83441.
[281] Buenemann M, Lenz P. Elastic properties and mechanical stability of chiral and
lled viral capsids. Phys Rev E 2008;78:21.
80 M.P. Neubauer et al. / Advances in Colloid and Interface Science 207 (2014) 6580
[282] Arkhipov A, Freddolino PL, Imada K, Namba K, Schulten K. Coarse-grained molecular
dynamics simulations of a rotating bacterial agellum. Biophys J 2006;91:458997.
[283] Arkhipov A, Freddolino PL, Schulten K. Stability and dynamics of virus capsids de-
scribed by coarse-grained modeling. Structure 2006;14:176777.
[284] Arkhipov A, Yin Y, Schulten K. Four-scale description of membrane sculpting by
BAR domains. Biophys J 2008;95:280621.
[285] Yin Y, Arkhipov A, Schulten K. Simulations of membrane tubulation by lattices of
amphiphysin N-BAR domains. Structure 2009;17:88292.
[286] Alexeev A, Verberg R, Balazs AC. Modeling the motion of microcapsules on compli-
ant polymeric surfaces. Macromolecules 2005;38:1024460.
[287] Buxton GA, Verberg R, Jasnow D, Balazs AC. Newtonian uid meets an elastic solid:
coupling lattice Boltzmann and lattice-spring models. Phys Rev E 2005;71:16.
[288] Maresov EA, Kolmakov GV, Yashin VV, Van Vliet KJ, Balazs AC. Modeling the mak-
ing and breaking of bonds as an elastic microcapsule moves over a compliant sub-
strate. Soft Matter 2012;8:7785.
[289] Alexeev A, Verberg R, Balazs AC. Modeling the interactions between deformable
capsules rolling on a compliant surface. Soft Matter 2006;2:499509.
[290] Zhu GD, Alexeev A, Kumacheva E, Balazs AC. Modeling the interactions between
compliant microcapsules and pillars in microchannels. J Chem Phys 2007;127:10.
[291] Arkhipov A, Roos WH, Wuite GJL, Schulten K. Elucidating the mechanism behind ir-
reversible deformation of viral capsids. Biophys J 2009;97:20619.
[292] Cieplak M, Robbins MO. Nanoindentation of virus capsids in a molecular model. J
Chem Phys 2010;132:12.
[293] Carrasco C, Luque A, Hernando-Perez M, Miranda R, Carrascosa JL, Serena PA, et al.
Built-in mechanical stress in viral shells. Biophys J 2011;100:11008.
[294] Smets J, Sands PD, Guinebretiere SJ, Pintens A, Dihora JO. In: EP Ofce, editor. Benet
agent containing delivery particle., EP2094828B1; 2013 [Appleton Papers Inc].
[295] Guinebretiere SJ, Smets J, Sands PD, Pintens A, Dihora JO. In: EP Ofce, editor. Ben-
et agent-containing delivery particle., EP2087089B1; 2012 [The Procter and Gam-
ble Company].
[296] Mueller R, Kohler K, Weinkamer R, Sukhorukov G, Fery A. Melting of PDADMAC/
PSS capsules investigated with AFM force spectroscopy. Macromolecules
2005;38:976671.
[297] Kim BS, Fan TH, Vinogradova OI. Thermal softening of superswollen polyelectrolyte
microcapsules. Soft Matter 2011;7:27058.
[298] Elsner N, Kozlovskaya V, Sukhishvili SA, Fery A. pH-Triggered softening of
crosslinked hydrogen-bonded capsules. Soft Matter 2006;2:96672.
[299] Lulevich VV, Vinogradova OI. Effect of pH and salt on the stiffness of polyelectrolyte
multilayer microcapsules. Langmuir 2004;20:28748.
[300] Lebedeva OV, Kim BS, Vasilev K, Vinogradova OI. Salt softening of polyelectrolyte
multilayer microcapsules. J Colloid Interface Sci 2005;284:45562.
[301] Fernandes PAL, Delcea M, Skirtach AG, Mohwald H, Fery A. Quantication of release
from microcapsules upon mechanical deformation with AFM. Soft Matter
2010;6:187983.
[302] Delcea M, Schmidt S, Palankar R, Fernandes PAL, Fery A, Mohwald H, et al.
Mechanobiology: correlation between mechanical stability of microcapsules stud-
ied by AFM and impact of cell-induced stresses. Small 2010;6:285862.
[303] Bedard MF, Munoz-Javier A, Mueller R, del Pino P, Fery A, Parak WJ, et al. On the
mechanical stability of polymeric microcontainers functionalized with nanoparti-
cles. Soft Matter 2009;5:14855.
[304] Fery A, Tsukruk VV. Tailoring the mechanics of freestanding multilayers. In: Decher
G, Schlenoff J, editors. Multilayer thin lms: sequential assembly of nanocomposite
materials., 2nd ed., Vol. 1. Weinheim: Wiley; 2012.
[305] Beningo KA, Wang YL. Fc-receptor-mediated phagocytosis is regulated by mechan-
ical properties of the target. J Cell Sci 2002;115:84956.
[306] Liu WJ, Zhou XY, Mao ZW, Yu DH, Wang B, Gao CY. Uptake of hydrogel particles
with different stiffness and its inuence on HepG2 cell functions. Soft Matter
2012;8:923545.
[307] Banquy X, Suarez F, Argaw A, Rabanel JM, Grutter P, Bouchard JF, et al. Effect of me-
chanical properties of hydrogel nanoparticles on macrophage cell uptake. Soft Mat-
ter 2009;5:398491.
[308] Yi X, Shi XH, Gao HJ. Cellular uptake of elastic nanoparticles. Phys Rev Lett 2011;107:5.
[309] De Geest BG, Dejugnat C, Sukhorukov GB, Braeckmans K, De Smedt SC, Demeester J.
Self-rupturing microcapsules. Adv Mater 2005;17:2357.
[310] De Geest BG, Dejugnat C, Prevot M, Sukhorukov GB, Demeester J, De Smedt SC. Self-
rupturing and hollow microcapsules prepared from bio-polyelectrolyte-coated
microgels. Adv Funct Mater 2007;17:5317.
[311] Stubbe BG, Horkay F, Amsden B, Hennink WE, De Smedt SC, Demeester J. Tailoring
the swelling pressure of degrading dextran hydroxyethyl methacrylate hydrogels.
Biomacromolecules 2003;4:6915.
[312] De Geest BG, McShane MJ, Demeester J, De Smedt SC, Hennink WE. Microcapsules
ejecting nanosized species into the environment. J Am Chem Soc 2008;130:14480.
[313] De Cock LJ, De Koker S, De Geest BG, Grooten J, Vervaet C, Remon JP, et al. Polymeric
multilayer capsules in drug delivery. Angew Chem Int Edit 2010;49:695473.
[314] Bedard MF, De Geest BG, Moehwald H, Sukhorukov GB, Skirtach AG. Direction spe-
cic release from giant microgel-templated polyelectrolyte microcontainers. Soft
Matter 2009;5:392731.
[315] Schmidt S, Fernandes PAL, De Geest BG, Delcea M, Skirtach AG, Mohwald H, et al.
Release properties of pressurized microgel templated capsules. Adv Funct Mater
2011;21:14118.
[316] Qin SP, Caskey CF, Ferrara KW. Ultrasound contrast microbubbles in imaging and
therapy: physical principles and engineering (vol 54, pg R27, 2009). Phys Med
Biol 2009;54:4621.
[317] De Jong N, Bouakaz A, Frinking P. Basic acoustic properties of microbubbles. Echo-
cardiography 2002;19:22940.
[318] Marmottant P, van der Meer S, Emmer M, Versluis M, de Jong N, Hilgenfeldt S, et al.
A model for large amplitude oscillations of coated bubbles accounting for buckling
and rupture. J Acoust Soc Am 2005;118:3499505.
[319] Poehlmann M, Grishenkov D, Kothapalli SVVN, Harmark J, Hebert H, Philipp A, et al.
On the interplay of shell structure with low and high frequency mechanics of mul-
tifunctional magnetic microbubbles. Soft Matter 2013. http://dx.doi.org/10.1039/
c3sm51560e.
[320] Cavalieri F, Finelli I, Tortora M, Mozetic P, Chiessi E, Polizio F, et al. Polymer
microbubbles as diagnostic and therapeutic gas delivery device. Chem Mater
2008;20:32548.
[321] Yang F, Chen P, He W, Gu N, Zhang XZ, Fang K, et al. Bubble microreactors triggered
by an alternating magnetic eld as diagnostic and therapeutic delivery devices.
Small 2010;6:13005.
[322] Kiessling F, Fokong S, Koczera P, Lederle W, Lammers T. Ultrasound microbubbles
for molecular diagnosis, therapy, and theranostics. J Nucl Med 2012;53:3458.
[323] Shchukin DG, Gorin DA, Moehwald H. Ultrasonically induced opening of polyelec-
trolyte microcontainers. Langmuir 2006;22:74004.
[324] Dubreuil F, Shchukin DG, Sukhorukov GB, Fery A. Polyelectrolyte capsules modied
with YF3 nanoparticles: an AFM study. Macromol Rapid Commun 2004;25:107881.
[325] Kolesnikova TA, Gorin DA, Fernandes P, Kessel S, Khomutov GB, Fery A, et al. Nano-
composite microcontainers with high ultrasound sensitivity. Adv Funct Mater
2010;20:118995.
[326] Lensen D, Gelderblom EC, Vriezema DM, Marmottant P, Verdonschot N, Versluis M,
et al. Biodegradable polymeric microcapsules for selective ultrasound-triggered
drug release. Soft Matter 2011;7:541722.
[327] Pavlov AM, Saez V, Cobley A, Graves J, Sukhorukov GB, Mason TJ. Controlled protein
release from microcapsules with composite shells using high frequency
ultrasound-potential for in vivo medical use. Soft Matter 2011;7:43417.
[328] Yang QY, Chen JF, Wang LB, Xu Q, He LH. Morphology control and 2D self-assembly of
poly(styrene-co-divinylbenzene) capsules. J Colloid Interface Sci 2011;358:43743.
[329] Zhang YF, Lu T, Zeng XP, Zhou HJ, Guo HX, Bonaccurso E, et al. Surface-mediated
buckling of core-shell spheres for the formation of oriented anisotropic particles
with tunable morphologies. Soft Matter 2013;9:258992.
[330] Wilson DA, Nolte RJM, van Hest JCM. Autonomous movement of platinum-loaded
stomatocytes. Nat Chem 2012;4:26874.
[331] Elsner N, Dubreuil F, Fery A. Tuning of microcapsule adhesion by varying the
capsule-wall thickness. Phys Rev E 2004;69.
[332] Seifert U, Lipowsky R. Adhesion of vesicles. Phys Rev A 1990;42:476871.
[333] Graf P, Finken R, Seifert U. Adhesion of microcapsules. Langmuir 2006;22:71179.
[334] Wan KT, Liu KK. Contact mechanics of a thin-walled capsule adhered onto a rigid
planar substrate. Med Biol Eng Comput 2001;39:6058.
[335] Nolte M, Fery A. Coupling of individual polyelectrolyte capsules onto patterned
substrates. Langmuir 2004;20:29958.
[336] Yang J, Gao CY. Fabrication of diverse microcapsule arrays of high density and good
stability. Macromol Rapid Commun 2010;31:106570.
[337] Alexeev A, Verberg R, Balazs AC. Motion of compliant capsules on corrugated sur-
faces: a means of sorting by mechanical properties. J Polym Sci B Polym Phys
2006;44:266778.
[338] Alexeev A, Balazs AC. Designing smart systems to selectively entrap and burst mi-
crocapsules. Soft Matter 2007;3:15005.
[339] Smith KA, Alexeev A, Verberg R, Balazs AC. Designing a simple ratcheting system to
sort microcapsules by mechanical properties. Langmuir 2006;22:673942.
[340] Alexeev A, Verberg R, Balazs AC. Patterned surfaces segregate compliant microcap-
sules. Langmuir 2007;23:9837.
[341] Usta OB, Alexeev A, Balazs AC. Fork in the road: patterned surfaces direct microcap-
sules to make a decision. Langmuir 2007;23:1088790.
[342] Springman RM. Mechanical and chemical effects in adhesion of thin shell struc-
tures with applications in wafer bonding and adhesion of living cells. Philadelphia:
University of Pennsylvania; 2009.