Journal of Membrane Science 448 (2013) 231239

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Journal of Membrane Science

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

Mathematical modeling of molecular recognition by an ion-gating

membrane oscillator
Taichi Ito a, Hidenori Ohashi b, Takanori Tamaki b, Takeo Yamaguchi b,n
a
b

Center for Disease Biology and Integrative Medicine, The University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-0033, Japan
Chemical Resources Laboratory, Tokyo Institute of Technology, Nagatsutacho 4259, Midori-ku, Yokohama, Kanagawa 226-8503, Japan

art ic l e i nf o

a b s t r a c t

Article history:
Received 13 February 2013
Received in revised form
30 June 2013
Accepted 2 August 2013
Available online 13 August 2013

A mathematical model to explain the mechanism of molecular recognition by an ion-gating membrane

oscillator has been proposed, in which the hydrostatic pressure-driven ow (pore-open state) and
osmotic ow (pore-closed state) are switched alternatively in response to a specic ion signal. The model
was based on transport equations derived from nonequilibrium thermodynamics, where the dependency
of the reection coefcient and the solvent hydrostatic permeability on the signal ion concentration were
assumed to follow the Hill equation, based on experimental data. A time-delay effect was also introduced
into the permeation parameters by rst derivation. As a result, the model reproduced the characteristic
parameters of the oscillator, such as the period and amplitude. It also claried that an autocatalytic
process, the key for nonlinear oscillation, was generated for an osmotic period by a slow response of the
reection coefcient and a fast response of the solvent hydrostatic permeability, i.e., the osmotic ow
removes the signal ions out of the membrane to the ion-fed side, which increases the osmotic ow, and
then more ions are removed from the membrane on opening the pores from the solvent side of the
membrane.
& 2013 Elsevier B.V. All rights reserved.

Keywords:
Molecular recognition
Membrane oscillator
Nonequilibrium thermodynamics
Mathematical modeling

1. Introduction
Nonlinear phenomena are observed in various elds, from
biosystems [1], such as organs [2] and cells [35], to articial
engineering systems, such as BZ reactions [69], chemical reactions on catalysts [10,11] or electrodes [12], and hydrogels [1316].
They can create unique patterns and/or rhythms [17], which confer
a high degree of functionality to each system. In particular, various
membrane systems [1823] are an interesting research eld for
nonlinear science, because they are an interface that separates two
different spaces having different chemical potentials. Mass transport can occur through them, and sometimes reactions are
coupled to these transport phenomena.
As one of such membrane system, a new nonlinear oscillator
shown in Fig. 1 [24] was fabricated, which is called an ion-gating
membrane oscillator for molecular recognition, inspired by the
Teorell oscillator [25,26]. Utilizing the swelling and shrinking of a
grafted copolymer of N-isopropylacrylamide and Benzo-18-crown6-acrylamide [27] inside the pores, the gating membrane could
control the osmotic pressure [28] and hydrostatic pressure-driven
ow [29] by opening and closing its pores in response to the
concentration of a signal ion, such as Ba2 . This gating membrane

Corresponding author. Tel.: 81 45 924 5254; fax: 81 45 924 5253.

E-mail address: yamag@res.titech.ac.jp (T. Yamaguchi).

0376-7388/$ - see front matter & 2013 Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.memsci.2013.08.001

was placed between a solvent chamber and a solution chamber.

A capillary was attached to the solution chamber, which was lled
with an aqueous ion solution. Thus, the resulting osmotic inow
from the solvent chamber increased the water level in the
capillary. In the case of Ba2 , the Ba2 ions entered the membrane
under hydrostatic ow, and then the pores closed and stopped
the hydrostatic ow. The water level in the capillary decreased at
the same time. After the pores closed, an osmotic ow generated
by the Donnan potential. Then the osmotic ow passed through
the membrane in the opposite direction to the hydrostatic ow.
This osmotic ow eliminated any complexed ions from the
membrane. At the same time, the water level in the capillary
gradually increased. When all the captured ions were eliminated,
the pores of the membrane then reopened, and a hydrostatic ow
reentered the membrane. This cycle could be repeated without
any external stimuli, and therefore a nonlinear self-excited oscillation occurred [24]. For comparison, other ions, such as Ca2 , did
not form complexes with the membrane. Consequently, in those
circumstances the membrane did not generate an osmotic ow,
and no oscillation occurred.
In general, mathematical modeling is an effective approach to
clarify the essential mechanism of nonlinear phenomena [30]. For
example, the HodgkinHuxley model [31,32] is a representative
model for showing the dynamic mechanism of the excitation of a
nerve system due to the active potential through a cellular membrane,
which is the driving force of the oscillation. Another typical example

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T. Ito et al. / Journal of Membrane Science 448 (2013) 231239

Fig. 1. A schematic drawing of the operation of molecular recognition by a gating membrane oscillator. The hydrostatic ow and the osmotic ow are generated alternatively
by the opening and closing of the pores.

is the van der Pol equation [30,33]. This equation can be used to
describe many systems, such as a tunnel diode oscillator. The
equation contains a so-called negative resistance, which also
generates an autocatalytic process. These models are ordinal
differential equation models, which can simplify nonlinear phenomena and clarify an essential character of the oscillation
dynamics, such as an autocatalytic or feedback process.
Nonequilibrium thermodynamics are useful for modeling
membrane oscillators [3436]. In addition, it is very convenient
to reduce equations to an ordinal differential system, such as the
van der Pol equation or the HodgkinHuxley model, to clarify an
oscillation mechanism. In the case of the Teorell oscillator, this was
specically based on nonequilibrium thermodynamics [25,26].
Assuming that the electrical resistance is a function of the solvent
ow and has a rst-order time-delay effect, Teorell reduced the
three simultaneous equations of the solvent ow, the solute ow,
and the electric current to an equation of the van der Pol type.
Although some inaccurate points about the modeling were
pointed out, and improved and/or modied models have been
suggested [37,38], the Teorell model shows that an approach based
on nonequilibrium thermodynamics is still efcient today, especially when the physicochemical details are unknown [39,40].
In this study, a molecular recognition by an ion-gating membrane oscillator is modeled based on nonequilibrium thermodynamics, the nonlinear relationships between the permeability
parameters of the steady state, the concentration of a signal ion
derived from an experimental approach, and any time-delay
effects introduced by the response rate of the permeability
parameters. The mechanism by which an autocatalytic process
occurs is discussed based on the model.

thickness100 m) was used as a substrate, and the plasma treatment power and time were 30 W and 1 min, respectively. The
membrane used, which had a grafted density of 1.01 mg/cm2, was
the same as the one used in the previously reported research [24,29].
2.2. Osmotic pressure and osmotic ow measurements
The osmotic pressure was measured using an osmometer cell at
43 1C, as described in an earlier publication [29]. The osmometer
had a solution chamber and a solvent chamber. The membrane
was placed between these two chambers. The solution chamber
was lled with an ion solution and was closed using a valve to
prevent the inow of solvent. The increase in pressure inside the
solution chamber was detected by a pressure sensor (Keyence, AP12A, Japan). The initial condition of the gating membrane was
changed by immersing the membrane in aqueous BaCl2 solutions
of various concentrations. The osmotic pressure was always
measured when the initial condition of the gating membrane
was 0 mM, as described in the previous publications. The osmotic
ow was measured using the same apparatus at 43 1C without
closing the valve, and the ux of poured solution was measured.

3. Model
3.1. Equations of membrane transport based on nonequilibrium
thermodynamics
Katchalsky derived the equations of membrane transport based
on nonequilibrium thermodynamics as follows [34]:
J v LP Ps ;

2. Experimental
2.1. Membrane preparation
The membranes were prepared by a graft polymerization method
using a peroxide plasma, as described in an earlier publication [28].
Briey, a porous high-density polyethylene lm (pore size0.2 m,

and
J s PC m C p 1scs J v ;

where J v and J s are the ux of the solvent and the solute, respectively.
The terms LP and s are the permeability of pure water and the
reection coefcient, respectively. The terms P, , P, C m , C p , and
cs are the solute permeability, the difference in osmotic pressure,

T. Ito et al. / Journal of Membrane Science 448 (2013) 231239

the difference in pressure, the concentration of solute on the fed side

of the membrane, the concentration of solute on the permeated side
of the membrane, and the average concentration of solute inside the
membrane, respectively.
Experimentally, the diffusive ux of the ions was much smaller
than the advective ux in Eq. (2), and thus, the rst term,
PC m C p , can be neglected:
J s 1scs J v 1scs LP Ps :

The inside of the membrane is assumed to be a continuously

stirring tank reactor, and neglected the ion concentration distribution inside the membrane. In this case, the concentration of the
ion inside the gating membrane can be represented by the average
ion concentration inside the membrane, c. Then, the mass balance
of the ions in the membrane can be represented as follows:
V

dc
Am J s_in J s_out ;
dt

233

these change in response to c, the ion concentration inside the

membrane. The value of LP decreases with an increase in c, while
the value of s increases with an increase in c. A nonlinear
relationship existed between LP , s, and c, is assumed based on
Hill's equation in the steady state, by reference to the experimental data. Hill's equation is known to describe the cooperative
binding effect of hemoglobins to oxygen in biochemistry eld. It is
generally used to determine nonlinear relationship based on
experimental data in various elds such as muscle mechanics
[42]. In the present research, the experimental data shown in
Figs. 2 and 5 are well tted by Hill's equations as mentioned
below. Thus, Hill's equation is introduced in Eqs. (11) and (12). It is
an important future work to clarify the relationship between ion
concentration, swelling and shrinking of the grafted copolymer

where V and Am are the pore volume of the membrane and the
area of the membrane, respectively, and J s_in and J s_out are the ion
uxes of the inow and the outow.
In the case of J s_in , the value of cs is equal to the ion
concentration of the inow solution from outside the membrane
(term cin in Eq. (3)). The direction of the ow switched alternatively between the osmotic period and the hydrostatic period. In
the osmotic period, the value of J s_in was negative and the
ion concentration of the inow solution, cin , was equal to the fed
ion concentration in the feed chamber, cf . On the other hand, in
the hydrostatic period, the value of J s_in was positive, and the ion
concentration of the inow solution, cin , was equal to zero in the
solvent chamber. Thus, Eq. (3) is reduced to
J s_in 1scin LP jPs j;

where
at Ps 4 0 : cin cf
at Ps r 0 : cin 0

Fig. 2. Determination of LP1 as a function of c by tting Hill's equation. The open

squares denote the experimental values previously reported in Ref. [24]. The solid
line is the determined function.

In the case of J s_out , the value of cs is equal to the ion

concentration inside the membrane as follows:
J s_out 1sc LP jPs j:

In Eqs. (2) and (3), the value of cs is constant, because the

equation depicts the steady state. In this study, the ion concentration inside the gating membrane changed, and thus cs was
replaced by c. Combining Eqs. (4)(6), the equation of ion transport was derived as follows:
V


dc
Am 1scin cLP U Ps j:
dt

The mass balance of the solvent also needs to be considered.

The change in solvent volume in the capillary is equal to the inow
or outow of the solvent through the membrane.
Ac dP
Am Lp Ps ;
g dt

where Ac and gare the cross-sectional area of the capillary and the
acceleration due to gravity, respectively.
3.2. Nonlinear relationship between the permeability parameters
and the ion concentration
The terms LP and s are the transport coefcients of the
membrane. These are usually constants in the case of separation
membranes, such as ultraltration membranes, because the membrane properties, such as the pore size and the density of xed
charges, are constant. However, in the case of a gating membrane,

Fig. 3. The dependency of the osmotic pressure on the initial ion concentration
inside the gating membrane. The ion concentrations of the feed ion and solvent
chamber were 100 and 0 mM, respectively. The initial ion concentration inside the
gating membrane was 0 mM (A), 40 mM (B), 100 mM (C), and 150 mM (D).

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T. Ito et al. / Journal of Membrane Science 448 (2013) 231239

Table 1
Parameters used in the numerical simulations.

Fig. 4. Osmotic ux for various feed ion concentrations between 0 and 100 mM.
The initial ion concentration was xed at 0 mM for all conditions.

Parameter

Unit

Value

Predetermined parameters
Ac
Am
cf

m2
m2
mM
kPa
m3

1.5  10  5
1.4  10  3
40
105
8.2  10  8

Parameters estimated by auxiliary experiments

a

b
c1
mM
c2
mM
c3
mM
L0
m3 m  2 s  1(kPa)  1
m

s0

6.0  10  3
1
30
30
5
1.1  10  6
4
5
9.0  10  1

Fitting parameters for oscillation calculation

s (osmotic period)
s
s (hydrostatic period)
s
Lp (osmotic period)
s
s
Lp (hydrostatic period)

3600
3600
900
1

where Lp and s are the characteristic times of the hydrostatic

period and the osmotic period.
s1 s0

cc3 =c2 m
;
b cc3 =c2 m

11

and



c=c1 n
;
Lp1 L0 1
a c=c1 n

12

where L0 , s0 , c1 , c2 , c3 , a, b, n, and m are the tting parameters.

3.3. Equations of state of the oscillator and numerical calculations

Fig. 5. Determination of s1 as a function of c by tting Hill's equation. The open

squares are experimental values calculated from data in Fig. 4 using Eq. (17). The
solid line is the determined function for m 4. The dasheddotted line and the
dotted line are the cases for m 2 and 10, respectively, without changing the other
parameters of Hill's equation.

Simultaneous equations comprised of Eqs. (7)(12) represent

molecular recognition by the ion-gating membrane oscillator. The
representative parameter set is shown in Table 1. The previous
oscillations experiments were performed from the pore-opening
state with no ions inside the gating membrane. Thus, the initial
values of P, c, Lp , and s were 1.5 kPa, 0 mM, 1.1  10  6 m3 m  2
s  1(kPa)  1, and 0, respectively. The equations were solved
numerically using the RungeKutta method employing the C
software package. The effect and sensitivity of parameters such as
cf , Lp , s , and m on the computations were studied.

4. Results and discussion

4.1. Determination of LP1 as a function of c

inside the pores of the membrane, the pore size of the membrane,
and the ux values. In addition, as discussed in the following
section in detail, LP and s are assumed to have a rst-order timedelay effect. Thus, the steady-state values of LP and s, LP1 and s1 ,
respectively, were determined from a Hill's equation-type relationship. The values of LP and s were determined according to the
following equations:

The value of LP1 needed to be determined as a function of c for

the modeling. The experimental values of LP1 at various ion
concentrations have already been reported, as shown in Fig. 2
[28]. Eq. (12) is tted to the data shown in Fig. 2, and the tting
parameters are determined, as shown in Table 1.

ds 1
s1 s;
dt s

4.2. Dependency of osmotic pressure on the initial ion concentration

inside the gating membrane

10

Fig. 3 shows the time course of the osmotic pressure for

different initial concentrations of Ba2 ions inside the membrane.
The initial concentrations of curves (A), (B), (C), and (D) in Fig. 3 of

and
dLp
1

L L ;
dt
Lp p1 p

T. Ito et al. / Journal of Membrane Science 448 (2013) 231239

the gating membrane are 0, 40, 100, and 150 mM, respectively. The
feed ion concentration was 100 mM for all conditions, and so the
driving force of the osmotic pressure generation had the same
value. Thus, the osmotic pressure for a period of several hours
after starting a measurement was constant for all conditions.
However, the osmotic pressure in the early stages of the
measurements was different for each condition. The osmotic
pressure increased rapidly when the initial ion concentration
inside the gating membrane was lower than the feed ion concentration of 100 mM in the cases of curves (A) and (B). The pores of a
solvent-fed side can open, which would make it possible for a
rapid diffusion of water through the membrane. On the other
hand, the pores can close on the ion-fed side immediately after
measurements are commenced, because of the ions diffusing into
the gating membrane. In general, the existence of a very thin layer
that can reject the diffusion of a solute is adequate to generate an
osmotic pressure.
On the other hand, the osmotic pressure increased gradually
when the initial ion concentration inside the gating membrane
was higher than the feed ion concentration of 100 mM in the case
of curves (C) and (D). The pores of the gating membrane were
initially closed at a given point in the membrane. Thus, water
diffusion could be slower when compared with the case of curves
(A) and (B), which would result in a slow increase in the osmotic
pressure.
The period of this oscillation as reported in the previous
research was between 10 and 25 min [24]. Thus, the ion concentration inside the gating membrane may have a strong effect on
the oscillation. The ion concentration prole throughout the
directional thickness of the membrane reects the pore size prole
throughout that thickness. In addition, the pore size prole should
be considered as the key factor inuencing the oscillations.
4.3. Determination of s1 as a function of c by measuring the
osmotic ux
Fig. 4 shows the osmotic ux for a feed ion concentration
between 0 and 100 mM. The osmotic ux depended on the feed
ion concentration, because of the difference in the driving force for
the generation of the osmotic pressure; this was generated for a
feed ion concentration above 20 mM, which agrees well with the
previous osmotic pressure data [24].
The initial ion concentration inside the gating membrane was
xed at 0 mM for all conditions, because the concentration inside
the membrane, which is dened as the value of c in Eq. (7), must
decrease and the pores of the gating membrane must open each
time the osmotic period switched into the hydrostatic period in
the oscillator. This means that osmotic ux when the ion concentration inside the gating membrane was 0 mM is an important
parameter. The osmotic ux decreased with time and became
almost constant 4 h after commencing the measurements shown
in Fig. 4. This coincided well with the osmotic pressure of curve
(A) in Fig. 3.
Based on these considerations, the osmotic ux was dened as
the value measured 10 min after the commencement of the
measurements, because the period of this oscillation as reported
in the previous research was between 10 and 25 min [24]. The
equations of membrane transport, Eqs. (13) and (14), can be
derived from linear response theory as follows [34]:
J v LP P LPD ;

13

and
J D LDP P LD ;

14

where J v and J D are the hydrostatic pressure-driven ow and the

diffusive ow, and LP , LPD , LDP , and LD are proportionality coefcients.

235

The value of LPD was determined from the measured osmotic ux

using Eq. (15), because P 0 in Eq. (13):
LPD

Jv

15

Katchalsky dened s as follows:

LPD
s
LP

16

Thus, the following relationship holds for the research:

s1 

LPD
LP1

17

The value of LP1 was reported in the earlier publication [28],

and is shown in Fig. 2. Hence, s1 was calculated for each feed ion
concentration using Eq. (17), as shown in Fig. 5. In the modeling
calculations, Eq. (11) was tted to the data, and the parameters
were determined, as shown in Table 1. The parameter m is an
important parameter, and a value of m 4 tted the data well. In
addition, in Fig. 5, the lines for other values of m are drawn,
without changing the other parameters in Eq. (17), for use in
further discussion.
4.4. Reproduction of the capillary water pressure of the oscillator
using numerical calculations
Numerical simulations were performed using all the determined parameters, as summarized in Table 1. The parameters of
the membrane and capillary, V, Am , and Ac , were determined from
calculations using the experimental data shown in Table 1. The
value of cf at which oscillations were observed experimentally was
40 mM, as reported in the previous publication [24]. The osmotic
pressure, , was calculated using van't Hoff's law from the value
of cf . The characteristic times of the hydrostatic period and the
osmotic period, Lp and s , were assigned for both the osmotic and
hydrostatic periods without obtaining experimental values, as
shown in Table 1. The value of Lp and s were signicantly
different, where s is much higher than Lp . The response rate of
the membrane to change the hydrostatic pressure-driven ux in
response to the BaCl2 concentration was extremely fast as reported
in the previous study. In fact, the pores closed below 30 s [41].
Partially because Ba2 was fed to the membrane by pressuredriven ux. On the other hand, the characteristic time of the
generation of osmotic pressure was ca. 60 min as shown in
Figs. 3 and 4. Therefore, Lp was assumed as 1 s in the hydrostatic
period or 900 s in the osmotic period, while s was assumed as
3600 s.
Fig. 6 shows the time course of a simulated capillary water
pressure, where the value of P in Eq. (8) was equal to the water
level of the attached capillary. The value of P showed a nonlinear
oscillation with an amplitude of about 0.1 kPa for a period of about
20 min. The simulated amplitude and period of P were commensurate with the experimental values. (The experimental data
[24] are available in the Supplementary information.) The oscillation was nally dampened at P 18.7 kPa in the model, which is
similar to the experimental value, because the oscillation appeared
as a transitional phenomenon. The wave forms obtained for
different values of P are also shown in Fig. 6(B) and (C) from
magnied sections of Fig. 6(A). These showed a slow decrease in
P in the hydrostatic period for low values of P. However,
they showed a sharp decrease in P in the hydrostatic period for
high values of P. Similar change in the waveforms with increasing values of P was also observed in the experiments.
The proposed model captures well the essential mechanism of
molecular recognition in an ion-gating membrane oscillator, based
on the above comparison between the experiment data available

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T. Ito et al. / Journal of Membrane Science 448 (2013) 231239

Fig. 7. (A) The time course of the ion concentration inside the gating membrane, c,
from numerical calculations. The parameters used for the numerical calculations
are shown in Table 1. The concentration of the fed ion, cf , was 100 mM (A), 40 mM
(B), 20 mM (C), and 10 mM (D). Only (A) and (B) generated an oscillation of the ion
concentration inside the gating membrane. (B) The time course of LP and s from
numerical calculations. The parameters used for the numerical calculations are
shown in Table 1. The concentration of the fed ion, cf , was 40 mM. An autocatalytic
increase in LP was observed during the osmotic period.

Fig. 6. Reproduction of the capillary water pressure of the oscillator by the

numerical calculations. The parameters used for the numerical calculations are
shown in Table 1. (A) An overall view. (B) Partially magnied at the time points
between 0.5 and 3.0 h. (C) Partially magnied at the time points between 45.0 and
47.0 h.

in the Supplementary information and the modeling results

shown in Fig. 6.
4.5. Clarication of autocatalytic process in the osmotic period based
on the model calculations
In general, an oscillator requires both an autocatalytic and a
feedback process. The autocatalytic process occurred during the
increase of water level in the case of the present oscillator.
Feedback occurred via the hydrostatic ow, which rapidly closed
the pores of the gating membrane by feeding ions into the
membrane. However, the autocatalytic process mechanism was
unclear, even qualitatively. The model makes it possible to suggest
a mechanism of the autocatalytic process.
Fig. 7(A) shows the time course of the ion concentration inside
the gating membrane, c. When the pores were open, c increased

sharply owing to the inow of the ion solution from the hydrostatic ow in the hydrostatic period. This increase in c rapidly
closed the pores because of the small value of Lp . If the autocatalytic process did not exist, then the pores would have been
kept in the intermediate state between open and closed, and no
oscillation would have occurred. However, the value of c began to
gradually decrease because the osmotic ow pushed out the ions
inside the gating membrane. Once the value of c decreased to a
given value, the value of LP began to increase sharply, as shown in
Fig. 7(B). This increase in the value of LP brought about an increase
in the osmotic ow, because the osmotic ow, J v , obeys Eq. (1). The
stronger the osmotic ow became, the more efciently the
osmotic ow pushed the ions out from the gating membrane.
The larger the decrease in c became, the stronger the osmotic ow
became. This autocatalytic process brought about the reopening of
the pores of the gating membrane. Once the pores were reopened,
the same phenomena occurred, and so the oscillation continued. It
should be noted that the change in the value of c depended on the
ion concentration of the feed solution, cf . When the value of cf was
low, as shown in curves (C) and (D) in Fig. 7(A), no oscillations
were observed.
A schematic diagram of this autocatalytic process in the
osmotic period is shown in Fig. 8 based on the modeling calculation results. The model suggests that LP increases and the value of

T. Ito et al. / Journal of Membrane Science 448 (2013) 231239

237

Fig. 8. A schematic drawing of the autocatalytic process in the osmotic period based on the numerical calculation results shown in Fig. 7. An autocatalytic increase in LP was
generated when the pores opened from the solvent chamber side. At the same time, the value of s was kept high during the process because of the thin layer on the solution
side when the pores were closed. Thus, the osmotic ow increased autocatalytically following Eq. (1).

s is kept high during the autocatalytic process. In general, in

membrane science, the value of LP depends on the membrane
thickness of a dense separation layer. However, the value of s does
not depend on the membrane thickness of a dense separation
layer. Hence, separation membranes have evolved from a symmetrical membrane structure into an asymmetrical membrane structure, which has a thin separation layer and a thick supportive
layer. An asymmetric membrane can achieve both a high selectivity and a high permeation ux, because of the compatibility of a
high value of LP and a high value of s. Based on this knowledge
well known in membrane science, the changes in LP and s in the
osmotic period are interpreted to be related to the pore size prole
throughout the directional thickness of the membrane, as shown
in Fig. 8. Owing to the osmotic ow, the pores began opening on
the pure water side of the gating membrane, which increased the
value of LP more and more. At the same time, the existence of a
very thin layer of closed pores on the feed ion side was enough to
maintain a high value of s. Thus, the membrane properties, such as
the amplitude and period of the oscillator, are considered to be
closely related to the thickness of the gating membrane.
The following point should be noted. The uctuation of s was
very small; however, oscillations were not observed without the
modulation of s(data not shown). This means that little change of
s is crucially important for the oscillations. That is to say, the
decrease of s in the osmotic period contributed to the increase of
J s_out in Eq. (6) as well as the change of LP .

4.6. The relationship between the gating effect of the membrane and
the generation of oscillations
The characteristic times, Lp and s , are important, because no
oscillations would occur if the time-delay effect was not assumed
in the model. Fig. 9(A) and (B) show the calculated values of P for
different values of Lp and s . Oscillations occurred over a wide
range of Lp and s . In addition, the period and amplitude both
depended on the values of Lp and s .
A limitation of the model was the assumption of Lp and s
without experimental proof of the values. Thus, the qualitative
relationship between the membrane structure and the oscillation
properties are difcult to be discussed. A physical meaning of
these characteristic times is the time-delay effect on LP and s,
which arises from the pore size prole throughout the membrane
thickness, as shown in Fig. 8. Thus, a large value of s in the

osmotic period corresponds to a large membrane thickness.

A normal membrane thickness is thought to exist for the oscillator.
The effect of s1 on the oscillations is also investigated. The
curvature of the relationship between s1 and c depends on
the parameter m in Eq. (12), as shown in Fig. 5. Fig. 10 shows
the calculated value of P for various values of m. The oscillations
were sensitive to the value of m. The pores closed at an ion
concentration inside the gating membrane of 20 mM. When m is
large, the pores of the gating membrane close rapidly and are
sensitive to the change in ion concentration around 20 mM. On the
other hand, the pores of the gating membrane close slowly in
response to a change in the ion concentration when the value of m
is small. The gating membrane did not generate oscillations both
for large values of m (m 10) and small values of m (m 2). This
means that the pores of the gating membrane needed to close
continuously in response to a change in the ion concentration. In
addition, the pores needed to close rapidly to some degree in
response to the change in ion concentration inside the membrane.
In the previous publication, the oscillations were generated by
experimental trial and error [24]. Through investigating the effect
of parameters such as Lp , s , and m, the structure and properties
of the gating membrane used in the previous research [24] were
optimized by chance for generating the oscillations. The structural
features of the gating membrane, such as the thickness, pore size,
and porosity of the substrate used, and amount and prole of the
grafting copolymer, determine the functions of the gating membrane that control the hydrostatic ow and the osmotic ow. Only
when these functions are properly combined are oscillations
observed.
In the earlier publication [24], the existence of a trace amount
of the additive 18-crown-6 was necessary to induce oscillations. It
should be noted that the model neglected any effect of this.
Besides this, the model suggested some important points for
consideration, such as the mechanism of the autocatalytic process
and the relationship between the gating function and the generation of oscillations. The phenomenological approach was useful for
the situation, in which the physical and chemical behavior of the
gating membrane was only partially claried.

5. Conclusions
A molecular recognition by an ion-gating membrane oscillator
has been mathematically modeled using membrane transport

238

T. Ito et al. / Journal of Membrane Science 448 (2013) 231239

Fig. 10. Inuence of the Hill's equation parameter m on the oscillation from
numerical calculations. The relevant value of m (m 4) can generate an oscillation
over a long period.

guidelines on how to design gating membranes for nonlinear

oscillation systems.

Appendix A. Supporting information

Supplementary data associated with this article can be found in
the online version at http://dx.doi.org/10.1016/j.memsci.2013.08.001.

Nomenclature
Ac
Am
a
b
c, cs
c1
c2
c3
cf
cin
cout
Cm
Cp
Fig. 9. Inuence of the characteristic times s and Lp on the oscillation from
numerical calculations. (A) Capillary water pressure at various characteristic times
in the osmotic period. (B) Capillary water pressure at various characteristic times in
the hydrostatic period.

equations based on nonequilibrium thermodynamics. A mechanism for the oscillator has been proposed based on numerical
solutions of the model. The autocatalytic increase in the pure
water permeability, LP , in the osmotic period is considered to be
the key characteristic of the oscillator. In addition, the oscillator is
extremely sensitive to the gating function of the membrane. The
sieving coefcient, s1 , depends on the ion concentration inside
the membrane. A slight difference in this dependency curve
greatly inuences the generation of the oscillations. The results
of the modeling calculations make a contribution to providing

g
JD
Jv
Js
J s_in
J s_out
L0
Lp
Lp1
LP
LPD
LDP
LD
m

cross-sectional area of capillary, m2

area of membrane, m2
parameter in Hill equation for Lp1 , dimensionless
parameter in Hill equation for s1 , dimensionless
average concentration of solute inside membrane,
mM
parameter in Hill equation for Lp1 , mM
parameter in Hill equation for s1 , mM
parameter in Hill equation for s1 , mM
ion concentration in feed chamber, mM
ion concentration of inow to the membrane, mM
ion concentration of outow from the membrane,
mM
solute concentration on fed side of membrane, mM
solute concentration on permeated side of membrane, mM
acceleration due to gravity, m  1 s  2
diffusive ux, mol m  2 s  1
hydrostatic pressure-driven ux of solvent,
m3 m  2 s  1
ux of solute, mol m  2 s  1
ion ux of inow to membrane, m3 m  2 s  1
ion ux of outow from membrane, m3 m  2 s  1
parameter in Hill equation for Lp1 ,
m3 m  2 s  1(kPa)  1
permeability of pure water, m3 m  2 s  1(kPa)  1
steady-state value of Lp , m3 m  2 s  1(kPa)  1
proportionality coefcient, m3 m  2 s  1(kPa)  1
proportionality coefcient, m3 m  2 s  1(kPa)  1
proportionality coefcient, mol m  2 s  1(kPa)  1
proportionality coefcient, mol m  2 s  1(kPa)  1
parameter in Hill equation for s1 , dimensionless

T. Ito et al. / Journal of Membrane Science 448 (2013) 231239

n
P

P
s0
V

parameter in Hill equation for Lp1 , dimensionless

solute permeability, m3 m  2 s  1
difference in pressure, kPa
parameter in Hill equation for s1 , dimensionless
pore volume of membrane, m3

Greek symbols

s
s1

Lp

difference in osmotic pressure, kPa

reection coefcient , dimensionless
steady-state value of s, dimensionless
characteristic time of s in osmotic/hydrostatic period,
s
characteristic time of Lp in osmotic/hydrostatic period,
s

Subscripts
c
f
in
Lp
m
out
p
s
s

capillary
feed solution
inow to membrane
permeability of pure water
membrane
outow from membrane
permeated solution
solute
reection coefcient

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