Red blood cell (RBC) deformability is important for tissue perfusion and a key determinant of blood rheology. Diseases such as diabetes, sickle cell anemia, and malaria, as well as prolonged storage, may affect the mechanical properties of RBCs altering their hemodynamic behavior and leading to microvascular complications. However, the exact role of RBC deformability on microscale blood flow is not fully understood. In the present study, we extend our previous work on healthy RBC flows in bifurcating microchannels [Sherwood et al., “Viscosity and velocity distributions of aggregating and non-aggregating blood in a bifurcating microchannel,” Biomech. Model. Mechanobiol. 13, 259–273 (2014); Sherwood et al., “Spatial distributions of red blood cells significantly alter local hemodynamics,” PLoS One 9, e100473 (2014); and Kaliviotis et al., “Local viscosity distribution in bifurcating microfluidic blood flows,” Phys. Fluids 30, 030706 (2018)] to quantify the effects of impaired RBC deformability on the velocity and hematocrit distributions in microscale blood flows. Suspensions of healthy and glutaraldehyde hardened RBCs perfused through straight microchannels at various hematocrits and flow rates were imaged, and velocity and hematocrit distributions were determined simultaneously using micro-Particle Image Velocimetry and light transmission methods, respectively. At low feed hematocrits, hardened RBCs were more dispersed compared to healthy ones, consistent with decreased migration of stiffer cells. At high hematocrit, the loss of deformability was found to decrease the bluntness of velocity profiles, implying a reduction in shear thinning behavior. The hematocrit bluntness also decreased with hardening of the cells, implying an inversion of the correlation between velocity and hematocrit bluntness with loss of deformability. The study illustrates the complex interplay of various mechanisms affecting confined RBC suspension flows and the impact of both deformability and feed hematocrit on the resulting microstructure.
REFERENCES
1.
J. M.
Sherwood
, E.
Kaliviotis
, J.
Dusting
, and S. H.
Balabani
, “Viscosity and velocity distributions of aggregating and non-aggregating blood in a bifurcating microchannel
,” Biomech. Model. Mechanobiol.
13
, 259
–273
(2014
).2.
J. M.
Sherwood
, D.
Holmes
, E.
Kaliviotis
, and S.
Balabani
, “Spatial distributions of red blood cells significantly alter local hemodynamics
,” PLoS One
9
, e100473
(2014
).3.
E.
Kaliviotis
, J. M.
Sherwood
, and S.
Balabani
, “Local viscosity distribution in bifurcating microfluidic blood flows
,” Phys. Fluids
30
, 030706
(2018
).4.
D. K.
Kaul
and R. L.
Nagel
, “Sickle cell vasoocclusion: Many issues and some answers
,” Experientia
49
, 5
–15
(1993
).5.
N.
Mohandas
and P. G.
Gallagher
, “Red cell membrane: Past, present, and future
,” Blood
112
, 3939
–3948
(2008
).6.
X.
Li
, E.
Du
, H.
Lei
, Y.-H.
Tang
, M.
Dao
, S.
Suresh
, and G. E.
Karniadakis
, “Patient-specific blood rheology in sickle-cell anaemia
,” Interface Focus
6
, 20150065
(2016
).7.
M.
Fornal
et al, “Erythrocyte stiffness in diabetes mellitus studied with atomic force microscope
,” Clin. Hemorheol. Microcirc.
35
, 273
–276
(2006
).8.
K.
Tsukada
, E.
Sekizuka
, C.
Oshio
, and H.
Minamitani
, “Direct measurement of erythrocyte deformability in diabetes mellitus with a transparent microchannel capillary model and high-speed video camera system
,” Microvasc. Res.
61
, 231
–239
(2001
).9.
S.
Shin
, Y.
Ku
, N.
Babu
, and M.
Singh
, “Erythrocyte deformability and its variation in diabetes mellitus
,” Indian J. Exp. Biol.
45
(1
), 121
–128
(2007
).10.
R.
Agrawal
et al, “Assessment of red blood cell deformability in type 2 diabetes mellitus and diabetic retinopathy by dual optical tweezers stretching technique
,” Sci. Rep.
6
, 15873
(2016
).11.
S.
Chien
, S.
Usami
, R. J.
Dellenback
, and M. I.
Gregersen
, “Blood viscosity: Influence of erythrocyte deformation
,” Science
157
, 827
(1967
).12.
S.
Chien
, “Shear dependence of effective cell volume as a determinant of blood viscosity
,” Science
168
, 977
–979
(1970
).13.
S.
Chien
, “Red cell deformability and its relevance to blood flow
,” Annu. Rev. Physiol.
49
, 177
–192
(1987
).14.
A. M.
Forsyth
, J.
Wan
, W. D.
Ristenpart
, and H. A.
Stone
, “The dynamic behavior of chemically ‘stiffened’ red blood cells in microchannel flows
,” Microvasc. Res.
80
, 37
–43
(2010
).15.
L.
Lanotte
et al, “Red cells’ dynamic morphologies govern blood shear thinning under microcirculatory flow conditions
,” Proc. Natl. Acad. Sci. U. S. A.
113
, 13289
–13294
(2016
).16.
S.
Chien
et al, “Rheology of sickle cells and its role in microcirculatory dynamics
,” Prog. Clin. Biol. Res.
240
, 151
–165
(1987
).17.
G. A.
Pantely
et al, “Increased vascular resistance due to a reduction in red cell deformability in the isolated hind limb of swine
,” Microvasc. Res.
35
, 86
–100
(1988
).18.
P.
Cabrales
, “Effects of erythrocyte flexibility on microvascular perfusion and oxygenation during acute anemia
,” Am. J. Physiol.-Heart Circ. Physiol.
293
, H1206
–1215
(2007
).19.
J. M.
Sosa
, N. D.
Nielsen
, S. M.
Vignes
, T. G.
Chen
, and S. S.
Shevkoplyas
, “The relationship between red blood cell deformability metrics and perfusion of an artificial microvascular network
,” Clin. Hemorheol. Microcirc.
57
, 275
–289
(2014
).20.
J. M.
Burns
et al, “Deterioration of red blood cell mechanical properties is reduced in anaerobic storage
,” Blood Transfus.
14
, 80
–88
(2016
).21.
D. K.
Wood
et al, “A biophysical indicator of vaso-occlusive risk in sickle cell disease
,” Sci. Transl. Med.
4
, 123ra26
(2012
).22.
J.
Dupire
, M.
Socol
, and A.
Viallat
, “Full dynamics of a red blood cell in shear flow
,” Proc. Natl. Acad. Sci. U. S. A.
109
, 20808
–20813
(2012
).23.
H. L.
Goldsmith
and J.
Marlow
, “Flow behaviour of erythrocytes. I. Rotation and deformation in dilute suspensions
,” Proc. R. Soc. London, Ser. B
182
, 351
–384
(1972
).24.
S.
Losserand
, G.
Coupier
, and T.
Podgorski
, “Migration velocity of red blood cells in microchannels
,” Microvasc. Res.
124
, 30
–36
(2019
).25.
X.
Grandchamp
, G.
Coupier
, A.
Srivastav
, C.
Minetti
, and T.
Podgorski
, “Lift and down-gradient shear-induced diffusion in red blood cell suspensions
,” Phys. Rev. Lett.
110
, 108101
(2013
).26.
D. A.
Fedosov
, B.
Caswell
, S.
Suresh
, and G. E.
Karniadakis
, “Quantifying the biophysical characteristics of Plasmodium-falciparum-parasitized red blood cells in microcirculation
,” Proc. Natl. Acad. Sci. U. S. A.
108
, 35
–39
(2011
).27.
J.
Zhang
, P. C.
Johnson
, and A. S.
Popel
, “Effects of erythrocyte deformability and aggregation on the cell free layer and apparent viscosity of microscopic blood flows
,” Microvasc. Res.
77
, 265
–272
(2009
).28.
P.
Bagchi
, “Mesoscale simulation of blood flow in small vessels
,” Biophys. J.
92
, 1858
–1877
(2007
).29.
T.
Sasaki
, J.
Seki
, T.
Itano
, and M.
Sugihara-Seki
, “Cross-sectional distributions of normal and abnormal red blood cells in capillary tubes determined by a new technique
,” Biorheology
54
, 153
–165
(2018
).30.
Z.
Shen
et al, “Inversion of hematocrit partition at microfluidic bifurcations
,” Microvasc. Res.
105
, 40
–46
(2016
).31.
B.
Namgung
, Y. C.
Ng
, H. L.
Leo
, J. M.
Rifkind
, and S.
Kim
, “Near-wall migration dynamics of erythrocytes in vivo: Effects of cell deformability and arteriolar bifurcation
,” Front. Physiol.
8
, 963
(2017
).32.
Y.
Chen
et al, “Margination of stiffened red blood cells regulated by vessel geometry
,” Sci. Rep.
7
, 15253
(2017
).33.
H.
Zhao
, E. S. G.
Shaqfeh
, and V.
Narsimhan
, “Shear-induced particle migration and margination in a cellular suspension
,” Phys. Fluids
24
, 011902
(2012
).34.
G.
Závodszky
et al, “Red blood cell and platelet diffusivity and margination in the presence of cross-stream gradients in blood flows
,” Phys. Fluids
31
, 031903
(2019
).35.
A.
Kumar
and M. D.
Graham
, “Mechanism of margination in confined flows of blood and other multicomponent suspensions
,” Phys. Rev. Lett.
109
, 108102
(2012
).36.
J. M.
Sherwood
, J.
Dusting
, E.
Kaliviotis
, and S.
Balabani
, “The effect of red blood cell aggregation on velocity and cell-depleted layer characteristics of blood in a bifurcating microchannel
,” Biomicrofluidics
6
, 024119
(2012
).37.
E.
Kaliviotis
, J. M.
Sherwood
, and S.
Balabani
, “Partitioning of red blood cell aggregates in bifurcating microscale flows
,” Sci. Rep.
7
, 44563
(2017
).38.
X.
Liu
et al, “The measurement of shear modulus and membrane surface viscosity of RBC membrane with Ektacytometry: A new technique
,” Math. Biosci.
209
, 190
–204
(2007
).39.
D. C.
Duffy
, J. C.
McDonald
, O. J. A.
Schueller
, and G. M.
Whitesides
, “Rapid prototyping of microfluidic systems in poly(dimethylsiloxane)
,” Am. Chem. Soc.
70
, 4974
–4984
(1998
).40.
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.
268
, H25
–H32
(1995
).41.
M. G.
Olsen
and R. J.
Adrian
, “Out-of-focus effects on particle image visibility and correlation in microscopic particle image velocimetry
,” Exp. Fluids
29
, S166
–S174
(2000
).42.
C.
Poelma
, A.
Kloosterman
, B. P.
Hierck
, and J.
Westerweel
, “Accurate blood flow measurements: Are artificial tracers necessary?
,” PLoS One
7
, e45247
(2012
).43.
44.
H. L.
Goldsmith
, “The microrheology of red blood cell suspensions
,” J. Gen. Physiol.
52
, 5
–28
(1968
).45.
J. J.
Bishop
, P. R.
Nance
, A. S.
Popel
, M.
Intaglietta
, and P. C.
Johnson
, “Effect of erythrocyte aggregation on velocity profiles in venules
,” Am. J. Physiol.-Heart Circ. Physiol.
280
, H222
–H236
(2001
).46.
D.
Fedosov
, “Multiscale modeling of blood flow and soft matter
,” Ph.D. thesis, Brown University
, 2010
.47.
M. K.
Lyon
and L. G.
Leal
, “An experimental study of the motion of concentrated suspensions in two-dimensional channel flow. Part 1. Monodisperse systems
,” J. Fluid Mech.
363
, 25
–56
(1998
).48.
M.
de Haan
et al, “Numerical investigation of the effects of red blood cell cytoplasmic viscosity contrasts on single cell and bulk transport behaviour
,” Appl. Sci.
8
, 1616
(2018
).49.
A.
Saadat
, C. J.
Guido
, and E. S. G.
Shaqfeh
, “Effect of cytoplasmic viscosity on red blood cell migration in small arteriole-level confinements
,” bioRxiv: 10.1101/572933 (2019
).50.
K.
Tatsumi
, S.
Noguchi
, A.
Tatsumi
, R.
Kuriyama
, and K.
Nakabe
, “Particle and red blood cell concentration distributions in narrow microchannel flows
,” Phys. Fluids
31
(8
), 082006
(2019
).51.
Q.
Meng
and J. J. L.
Higdon
, “Large scale dynamic simulation of plate-like particle suspensions. Part II: Brownian simulation
,” J. Rheol.
52
, 37
–65
(2008
).52.
E.
Kaliviotis
, D.
Pasias
, J. M.
Sherwood
, and S.
Balabani
, “Red blood cell aggregate flux in a bifurcating microchannel
,” Med. Eng. Phys.
48
, 23
–30
(2017
).53.
M.
Brust
et al, “Rheology of human blood plasma: Viscoelastic versus Newtonian behavior
,” Phys. Rev. Lett.
110
, 078305
(2013
).54.
S.
Varchanis
, Y.
Dimakopoulos
, C.
Wagner
, and J.
Tsamopoulos
, “How viscoelastic is human blood plasma?
,” Soft Matter
14
, 4238
–4251
(2018
).55.
J. G. G.
Dobbe
, G. J.
Streekstra
, M. R.
Hardeman
, C.
Ince
, and C. A.
Grimbergen
, “Measurement of the distribution of red blood cell deformability using an automated rheoscope
,” Cytometry
50
, 313
–325
(2002
).56.
H.
Schmid-Schönbein
and P.
Gaehtgens
, “What is red cell deformability?
,” Scand. J. Clin. Lab. Invest. Suppl.
156
, 13
–26
(1981
).57.
C. A.
Squier
, J. S.
Hart
, and A.
Churchland
, “Changes in red blood cell volume on fixation in glutaraldehyde solutions
,” Histochemistry
48
, 7
–16
(1976
).58.
F. M.
Morel
, R. F.
Baker
, and H.
Wayland
, “Quantitation of human red blood cell fixation by glutaraldehyde
,” J. Cell Biol.
48
, 91
–100
(1971
).59.
P. S.
Vassar
, J. M.
Hards
, D. E.
Brooks
, B.
Hagenberger
, and G. V.
Seaman
, “Physicochemical effects of aldehydes on the human erythrocyte
,” J. Cell Biol.
53
, 809
–818
(1972
).60.
O. K.
Baskurt
et al, “Comparison of three commercially available ektacytometers with different shearing geometries
,” Biorheology
46
, 251
–264
(2009
).61.
E.
Kaliviotis
, J.
Dusting
, J. M.
Sherwood
, and S.
Balabani
, “Quantifying local characteristics of velocity, aggregation and hematocrit of human erythrocytes in a microchannel flow
,” Clin. Hemorheol. Microcirc.
63
, 123
–148
(2016
).© 2019 Author(s).
2019
Author(s)
You do not currently have access to this content.