The physiological inflammation response depends upon the multibody interactions of blood cells in the microcirculation that bring leukocytes (white blood cells) to the vessel walls. We investigate the fluid mechanics of this using numerical simulations of 29 red blood cells and one leukocyte flowing in a two-dimensional microvessel, with the cells modeled as linearly elastic shell membranes. Despite its obvious simplifications, this model successfully reproduces the increasingly blunted velocity profiles and increased leukocyte margination observed at lower shear rates in actual microvessels. Red cell aggregation is shown to be unnecessary for margination. The relative stiffness of the red cells in our simulations is varied by over a factor of 10, but the margination is found to be much less correlated with this than it is to changes associated with the blunting of the mean velocity profile at lower shear rates. While velocity around the leukocyte when it is near the wall depends upon the red cell properties, it changes little for strongly versus weakly marginating cases. In the more strongly marginating cases, however, a red cell is frequently observed to be leaning on the upstream side of the leukocyte and appears to stabilize it, preventing other red cells from coming between it and the wall. A well-known feature of the microcirculation is a near-wall cell-free layer. In our simulations, it is observed that the leukocyte’s most probable position is at the edge of this layer. This wall stand-off distance increases with velocity following a scaling that would be expected for a lubrication mechanism, assuming that there were a nearly constant force pushing the cells toward the wall. The leukocyte’s near-wall position is observed to be less stable with increasing mean stand-off distance, but this distance would have potentially greater effect on adhesion since the range of the molecular binding is so short.

1.
T. A.
Springer
, “
Traffic signals on endothelium for lymphocyte circulation and leukocyte emigration
,”
Annu. Rev. Fluid Mech.
57
,
827
(
1995
).
2.
K. B.
Abbitt
and
G. B.
Nash
, “
Rheological properties of the blood influencing selectin-mediated adhesion of flowing leukocytes
,”
Am. J. Physiol. Heart Circ. Physiol.
285
,
H229
(
2003
).
3.
G. W.
Schmid-Schönbein
,
S.
Usami
,
R.
Skalak
, and
S.
Chien
, “
The interaction of leukocytes and erythrocytes in capillary and postcapillary vessels
,”
Microvasc. Res.
19
,
45
(
1980
).
4.
R. H.
Phibbs
, “
Distribution of leukocytes in blood flowing through arteries
,”
Am. J. Physiol.
210
,
919
(
1966
).
5.
T. W.
Secomb
, “
Mechanics of red blood cells and blood flow in narrow tubes
,” in
Modeling and Simulation of Capsules and Biological Cells
, edited by
C.
Pozrikidis
(
Chapman & Hall/CRC
,
Boca Raton
,
2003
), pp.
163
196
.
6.
R. J.
Melder
,
J.
Yuan
,
L. L.
Munn
, and
R. K.
Jain
, “
Erythrocytes enhance lymphocyte rolling and arrest in vivo
,”
Microvasc. Res.
59
,
316
(
2000
).
7.
H. L.
Goldsmith
and
S.
Spain
, “
Margination of leukocytes in blood flow through small tubes
,”
Microvasc. Res.
27
,
204
(
1984
).
8.
U.
Nobis
,
A. R.
Pries
,
G. R.
Coklet
, and
P.
Gaehtgens
, “
Radial distribution of white cells during blood flow in small tubes
,”
Microvasc. Res.
29
,
295
(
1985
).
9.
K. B.
Abbitt
and
G. B.
Nash
, “
Characteristics of leukocyte adhesion directly observed in flowing whole blood in vitro
,”
Br. J. Haematol.
112
,
55
(
2001
).
10.
J. C.
Firrell
and
H. H.
Lipowsky
, “
Leukocyte margination and deformation in mesenteric venules of rat
,”
Am. J. Physiol. Heart Circ. Physiol.
256
,
H1667
(
1989
).
11.
M. J.
Pearson
and
H. H.
Lipowsky
, “
Influence of erythrocyte aggregation on leukocyte margination in postcapillary venules of rat mesentery
,”
Am. J. Physiol. Heart Circ. Physiol.
279
,
H1460
(
2000
).
12.
M. J.
Pearson
and
H. H.
Lipowsky
, “
Effect of fibrinogen on leukocyte margination and adhesion in postcapillary venules
,”
Microcirculation (Philadelphia)
44
,
295
(
2004
).
13.
A. S.
Popel
,
P. C.
Johnson
,
M. V.
Kameneva
, and
M. A.
Wild
, “
Capacity for red blood cell aggregation is higher in athletic mammalian species than in sedentary species
,”
J. Appl. Physiol.
77
,
1790
(
1994
).
14.
C.
Sun
,
C.
Migliorini
, and
L. L.
Munn
, “
Red blood cells initiate leukocyte rolling in postcapillary expansions: a lattice Boltzman analysis
,”
Biophys. J.
85
,
208
(
2003
).
15.
C.
Sun
and
L. L.
Munn
, “
Particulate nature of blood determines macroscopic rheology: A 2-d lattice Boltzmann analysis
,”
Biophys. J.
88
,
1635
(
2005
).
16.
M. R.
King
,
D.
Bansal
,
M. B.
Kim
, and
I. H.
Sarelius
, “
The effect of hematocrit and leukocyte adherence on flow direction in the microcirculation
,”
Ann. Biomed. Eng.
32
,
803
(
2004
).
17.
C.
Migliorini
,
Y.
Qian
,
H.
Chen
,
E. B.
Brown
,
R. K.
Jain
, and
L. L.
Munn
, “
Red blood cells augment leukocyte rolling in a virtual blood vessel
,”
Biophys. J.
83
,
1834
(
2002
).
18.
C.
Pozrikidis
, “
Axisymmetric motion of a file of red blood cells through capillaries
,”
Phys. Fluids
17
,
031503
(
2005
).
19.
C.
Pozrikidis
, “
Numerical simulation of the flow-induced deformation of red blood cells
,”
Ann. Biomed. Eng.
31
,
1194
(
2003
).
20.
G.
Breyiannis
and
C.
Pozrikidis
, “
Simple shear flow of suspensions of elastic capsules
,”
Theor. Comput. Fluid Dyn.
13
,
327
(
2000
).
21.
G.
Kanzow
,
A. R.
Pries
, and
P.
Gaehtgens
, “
Analysis of the hematocrit distribution in the mesenteric micro-circulation
,”
Int. J. Microcirc.: Clin. Exp.
1
,
67
(
1982
).
22.
S. D.
House
and
H. H.
Lipowsky
, “
Microvascular hematocrit and red cell flux in rat cremaster muscle
,”
Am. J. Physiol. Heart Circ. Physiol.
252
,
H211
(
1987
).
23.
J. Q.
Lu
,
P.
Yang
, and
X.-H.
Hu
, “
Simulations of light scattering from a biconcave red blood cell using the finite-difference time-domain method
,”
J. Biomed. Opt.
10
,
024022
(
2005
).
24.
G. P.
Downey
,
D. E.
Doherty
,
B.
Schwab
 III
,
E. L.
Elson
,
P. M.
Henson
, and
G. S.
Worthen
, “
Retention of leukocytes in capillaries: role of cell size and deformability
,”
J. Appl. Physiol.
69
,
1767
(
1990
).
25.
R. L.
Whitmore
,
Rheology of the Circulation
(
Pergamon
,
Oxford
,
1968
).
26.
K.-M.
Jan
and
S.
Chien
, “
Role of surface electric charge in red blood cell interactions
,”
J. Gen. Physiol.
61
,
638
(
1973
).
27.
Y.
Suzuki
,
N.
Tateishi
, and
N.
Maeda
, “
Electrostatic repulsion among erythrocytes in tube flow, demonstrated by the thickness of the marginal cell-free layer
,”
Biorheology
35
,
155
(
1998
).
28.
C.
Pozrikidis
,
Boundary Integral and Singularity Methods for Linearized Viscous Flow
(
Cambridge University Press
,
Cambridge
,
1992
).
29.
C.
Canuto
,
M. Y.
Hussaini
,
A.
Quarteroni
, and
T. A.
Zang
,
Spectral Methods in Fluid Dynamics
(
Springer-Verlag
,
Berlin
,
1987
).
30.
H.
Hashimoto
, “
On the periodic fundamental solutions of the Stokes equations and their application to viscous flow past a cubic array of cylinders
,”
J. Fluid Mech.
5
,
317
(
1959
).
31.
D.
Frenkel
and
B.
Smit
,
Understanding Molecular Simulation
(
Academic Press
, San Diego) (
1996
).
32.
R. W.
Hockney
and
J. W.
Eastood
,
Computer Simulation Using Particles
(
Institute of Physics
,
Bristol
,
1988
).
33.
U.
Essemann
,
L.
Perera
,
M. L.
Berkowitz
,
T.
Darden
,
H.
Lee
, and
L. G.
Pedersen
, “
A smooth particle mesh Ewald method
,”
J. Chem. Phys.
103
,
8577
(
1995
).
34.
D.
Saintillan
,
E.
Darve
, and
E. S. G.
Shaqfeh
, “
A smooth particle-mesh Ewald algorithm for Stokes suspension simulations: The sedimentation of fibers
,”
Phys. Fluids
17
,
033301
(
2005
).
35.
E.
Metsi
, “
Large scale simulations of bidisperse emulsions and foams
,” Ph.D. thesis,
University of Illinois at Urbana-Champaign
(
2000
).
36.
M. E.
Staben
,
A. Z.
Zinchenko
, and
R. H.
Davis
, “
Motion of a particle between two parallel plane walls in low-Reynolds-number Poiseuille flow
,”
Phys. Fluids
15
,
1711
(
2003
).
37.
A. S.
Popel
and
P. C.
Johnson
, “
Microcirculation and hemorheology
,”
Annu. Rev. Fluid Mech.
37
,
43
(
2005
).
38.
D. S.
Long
, “
Microviscometric analysis of microvascular hemodynamics in vivo
,” Ph.D. thesis,
University of Illinois at Urbana-Champaign
, Urbana, Illinois (
2004
).
39.
R. J.
Melder
,
L. L.
Munn
,
S.
Yamada
,
C.
Ohkubo
, and
R. K.
Jain
, “
Selective- and integrin-mediated T-lymphocyte rolling and arrest on TNF-α-activated endothelium: augmentation by erythrocytes
,”
Biophys. J.
69
,
2131
(
1995
).
40.
W.
Reinke
,
P.
Gaehtgens
, and
P. C.
Johnson
, “
Blood viscosity in small tubes: effect of shear rate, aggregation and sedimentation
,”
Am. J. Physiol. Heart Circ. Physiol.
253
,
H540
(
1987
).
41.
C.
Alonso
,
A. R.
Pries
,
O.
Kiesslich
,
D.
Lerche
, and
P.
Gaehtgens
, “
Transient rheological behavior of blood in low-shear tube flow: velocity profiles and effective viscosity
,”
Am. J. Physiol. Heart Circ. Physiol.
268
,
H25
(
1995
).
42.
H. H.
Lipowsky
,
S.
Usami
, and
S.
Chien
, “
In vivo measurements of ‘apparent viscosity’ and microvessel hematocrit in the mesentry of the cat
,”
Microvasc. Res.
19
,
297
(
1980
).
43.
T. M.
Fisher
, “
A comparison of the flow behavior of disc shaped versus elliptic red blood cells (RBC)
,”
Blood Cells
4
,
453
(
1978
).
44.
G. P.
Krishnan
,
S.
Beimfohr
, and
D. T.
Leighton
, “
Shear-induced radial segregation in bidisperse suspensions
,”
J. Fluid Mech.
321
,
371
(
1996
).
You do not currently have access to this content.