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Research note
KEYWORDS
Plasmodium falciparum;
Red blood cell;
Blood flow;
Fluid dynamics;
Immersed boundary;
Lattice Boltzmann.
Abstract The mechanical properties of Red Blood Cells (RBCs) are influenced by invasion and occupation
of Plasmodium falciparum (Pf ). The corresponding variation results from the stiffening of RBCs and their
ability to adhere to endothelial cells. In this study, the transient deformation of Plasmodium falciparumparasitized red blood cell (Pf -RBC) has been studied numerically. The cell is modeled as deformable
liquid capsule enclosed by neo-Hookean elastic membrane. The effect of shear elasticity is included, but
bending stiffness is neglected. The numerical model is based on the immersed boundary-lattice Boltzmann
method (IB-LBM). The LBM is used to simulate fixed grid while the IBM is utilized to incorporate the
fluid-membrane interaction in a Lagrangian manner by a set of moving grids for membrane. The results
investigate the significance of elastic shear modulus and initial shape on hematocrit ratio and deformation
of Pf -RBC at different stages. The Pf -RBC at trophozoite and schizont stages obtain the lower hematocrit
ratio, as they become near-circular. The results are in good agreement with experiments and previous
studies. It appears, therefore, that the IB-LBM can be used to predict in vitro and in vivo studies of malaria.
2012 Sharif University of Technology. Production and hosting by Elsevier B.V. All rights reserved.
1. Introduction
Red Blood Cells (RBCs) are an important component in
blood because of their large number density (5 106 /mm3 ).
Being highly deformable particle, RBCs (approximately 40% of
blood volume) are primary cell species influencing rheological
properties of blood. RBC may exhibit reduced deformability
and stronger aggregation in many pathological situations, such
as heart disease, hypertension, diabetes, sickle cell anemia
and malaria [1]. Malaria is one of the most severe infection
diseases on earth. There are about five hundred million clinical
cases worldwide with more than two million deaths each
year [2]. The rheological properties and hemodynamic of blood
are changed by malaria infection. When a malaria parasite
invades and grows within a red blood cell, the structure
and biophysical characteristics of Pf -RBC are changed. The
1026-3098 2012 Sharif University of Technology. Production and hosting by Elsevier B.V. All rights reserved.
doi:10.1016/j.scient.2012.08.001
1330
Nomenclature
c
cs
ei
Es
fi
f eq
f
fs
f
F
Fi
HD
HT
P
Te
ni
nj
s
u
U
x
X
x
y
Greek symbols
t
x
density
weighting factor in direction i
relaxation time
stretch ratio
kinematic viscosity
delta function
Lattice time step
Lattice spacing
Subscripts
avg
1
2
s
c
i
average
in plane direction along the membrane
out of plane direction along the membrane
membrane elastic force at the Lagrangian coordinate
cell
direction
1
eq
fi (x, t ) fi (x, t ) ,
fi (x + ei t , t + t ) fi (x, t ) =
(1)
0 for i = 0
for i = 5, 6, 7, 8
eq
(2)
= Ei (, u),
(3)
Ei (, u) = i 1 +
ui e i
cs2
9
2
ui e i
cs2
3 u2
2 cs2
(4)
0 = 4/9
i = 1/36
i = 1/9
for i = 1, 2, 3, 4
for i = 5, 6, 7, 8.
(5)
fi ,
(6)
u=
ei fi .
1
=
cs2 t ,
(8)
(9)
eq
fi (x, t ) fi (x, t ) ,
fi (x + ei t , t + t ) = fi (x, t + t ),
1331
(7)
(10a)
(10b)
Initialize , u,
Initialize f = f eq ,
Streaming step,
Calculate u and by using Eqs. (6) and (7),
Calculate f eq from u and by using Eqs. (3) and (4),
Collision step.
1332
X ( s, t )
= u(X (s, t ), t ),
t
(11)
f ( x, t ) =
(12)
where:
1 1 + cos |r |
(r ) = 4
2
r 2
(13)
r > 2.
(14)
X
=
t
(15)
fi (x + ei t , t + t ) fi (x, t )
1
eq
fi (x, t ) fi (x, t ) + tFi
(16)
eq
fi = Ei (, u ),
1
u=
e i f i + f t ,
Fi =
(17)
(18)
i +
ei u
cs2
(ei u)
cs4
Te =
Es h
3/2
3 1 ,
(21)
(1) Impose the fluid velocity on the boundary and update the
boundary points positions to X (s, t ) by using Eq. (11).
(2) Calculate the force density F (s, t ) at the boundary points
from membrane stress by using Eq. (21).
(3) Spread the boundary point force F (s, t ) to the fluid external
force f (x, t ) by using Eq. (12).
(4) Calculate the LBMs external forcing terms Fi by using Eq.
(19).
(5) Perform Lattice Boltzmann equation evolution (Eq. (16)) to
obtain the distribution functions fi
(6) Calculate the fluid flow variables and u by Eqs. (6) and
(18).
ei f .
(19)
21
c0 + c1 x 2 + c2 x 4
1 < x < 1.
(20)
Simulations are carried out over a 100 300 rectangle in lattice units (20 m 60 m per lattice unit: x = 0.2 m) with
a single RBC. The simulation parameters based on experimentally determined data, are listed in Table 1. The bounce-back and
periodic boundary conditions are applied on the channel walls
and inlet/outlet, respectively [24].
The IBM algorithm ensures that there will be no relative
velocity between membrane and fluid, therefore no mass
transport across the membrane can occur and the volume of
RBC is naturally conserved. The results show that the change
in the enclosed RBC area is less than 1%.
Flow is generated by a pressure-gradient along the channel,
using the modified periodic boundary condition [27].The
pressure gradient, according to the Poiseuille law, will generate
a mean velocity of 7.5 mm/s for pure plasma flow without RBCs.
1333
Symbol
x
t
p
p
Es
H
L
P / x
Value
0.2 m
2.77 109 s
1.2 cP
1000 kg/m3
6.3 106 N/m
20 m
60 m
270 kPa/m
Figure 3: Evolutions of positions and shapes of the (a) healthy RBC, (b) ring
stage, (c) trophozite stage, and (d) schizont stage.
In this study, the cell morphological properties are determined, which are calculated based on the zero-, first-,
and second-order moments of cell shape, as proposed by Ma
et al. [16]. The details of the formulations are provided in the
Appendix. Extension, Mext , is a measure of how much the shape
differs from a circle. Extension of circle is zero and increases
without limit as the shape becomes less compact. Dispersion,
Mdis , expresses the difference between the shape of a 2D object
and its equimomental ellipse. It takes a value of zero, when the
shape is ellipse and increases with the irregularity of the object. To quantitatively illustrate the cell deformation, evolution
of extension and dispersion of centerline cells are presented
in Figures 4 and 5, respectively. The extension of the healthy
RBC and ring stage decreased slowly with time indicates that
they become more circular, since their sizes in x direction increase and their sizes in y direction decrease with time in order
to keep their areas fixed. The extension evolution of Pf -RBC in
thropozite and schizont stages is approximately similar to the
previous cases. Their dispersion increase with time for all cases,
1334
Figure 4: Temporal variations in the extension (a) healthy and ring stage RBC,
(b) trophozite and schizont RBC.
also the long axes of their equimomental ellipses are along perpendicular direction to the flow, similar to Ref. [16] in which
the dispersion of biconcave and circular centerline capsules
increases with time and the long axes of their equimomental ellipses are along y direction in the whole simulation time
range.
The Fahraeus effect [30] indicates that tube hematocrit in
microvessels (HT ) of less than 200 m is lower than supply
hematocrit (HD ). This is due to the fact that RBC mean velocity
is higher than mean fluid velocity. The velocity difference
originates from RBCs concentration in the center of the vessel. A
simple mass balance predicts the relation between hematocrit
ratio HT /HD and velocity ratio as:
HT
HD
Uav g
Uc
Figure 5: Temporal variations in the dispersion (a) healthy and ring stage RBC,
(b) trophozite and schizont RBC.
Figure 6: Evolution of the hematocrit ratios for healthy and different stages of
parasite development (ring, trophozeite, and schizont).
(22)
stages with healthy and ring stages. The hematocrit ratio is even
lower at trophozite and schizont stages where the Pf -RBC shape
becomes near-circular, i.e., the higher translational velocity.
The healthy and ring stage RBC have higher hematocrit ratios,
i.e., the lower translational velocity. Ma et al. [16] also found
that the biconcave capsule has higher hematocrit ratio with
respect to circular capsule. For schizont stage, the hematocrit
ratio in comparison with trophozite stage, increases with elastic
shear modulus, i.e. the capsule translational velocity decreases
with increasing elastic shear modulus, showing similar trend to
the centerline circular capsule in [16,18].
4. Conclusion
The transient motion and deformation of healthy and Pf RBC at different stages are studied in a two-dimensional
microchannel. The numerical simulation method is based on
m201
11 = 11 /m200
02 = /
2
02 m00
Ai = area,
i=1
xdxdy =
i =1
ydxdy =
i=1
x2 dxdy =
m02 =
S
Ai (xi + xi+1 ) ,
Ai (yi + yi+1 ) ,
1
i=1
m11 =
xydxdy
S
1
i =1
m20 =
S
1 = 20 + 02
2
2 = (20 02 )2 + 411
.
1 = 2 1 + 2
2 = 2 1 2 .
(A.5)
x2 dxdy =
6
i=1
(A.1)
(A.6)
mdis = log2
m01 =
(A.4)
Two second-order measures of shape that are invariant to rotation are expressed as:
m10 =
/m00 ).
20 = 20 /m200
mex = log(1 )
dxdy =
(A.3)
Based on the above variables, three normalized central moments, which are invariant to change in size of the 2D shape,
are given as follows:
Appendix
(A.2)
yc = m01 /m00 .
m00 =
1335
1 2 .
(A.7)
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Mehdi Navidbakhsh received his Ph.D. degree in 1996 from INPL (ENSEM),
France and is now Associate Professor of Mechanical Engineering at Iran
University of Science and Technology, Iran. His current research activities
include Simulation and Modeling in Biological System, Biofluid-Mechanics, CFD
and Cell Engineering.
Marzieh Rezazadeh received her M.Sc. degree from Mashhad University, Iran,
and is now a Ph.D. degree student of Mechanical Engineering at Iran University
of Science and Technology, Iran. Her main research interest includes work on
the numerical simulation of red blood cell in microchannel flow, numerical
methods such as control volume, lattice Boltzmann method, and immersed
boundary method.