Hostname: page-component-586b7cd67f-dlnhk Total loading time: 0 Render date: 2024-11-25T19:37:19.140Z Has data issue: false hasContentIssue false

The cell-free layer in simulated microvascular networks

Published online by Cambridge University Press:  11 February 2019

Peter Balogh
Affiliation:
Mechanical and Aerospace Engineering Department, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA
Prosenjit Bagchi*
Affiliation:
Mechanical and Aerospace Engineering Department, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA
*
Email address for correspondence: [email protected]

Abstract

In the microcirculation, a plasma layer forms near the vessel walls that is free of red blood cells (RBCs). This region, often termed as the cell-free layer (CFL), plays important haemorheological and biophysical roles, and has been the subject of extensive research. Many previous studies have considered the CFL development in single, isolated vessels that are straight tubes or channels, as well as in isolated bifurcations and mergers. In the body, blood vessels are typically winding and sequentially bifurcate into smaller vessels or merge to form larger vessels. Because of this geometric complexity, the CFL in vivo is three-dimensional (3D) and asymmetric, unlike in fully developed flow in straight tubes. The three-dimensionality of the CFL as it develops in a vascular network, and the underlying hydrodynamic mechanisms, are not well understood. Using a high-fidelity model of cellular-scale blood flow in microvascular networks with in vivo-like topologies, we present a detailed analysis of the fully 3D and asymmetric nature of the CFL in such networks. We show that the CFL significantly varies over different aspects of the networks. Along the vessel lengths, such variations are predominantly non-monotonic, which indicates that the CFL profiles do not simply become more symmetric over the length as they would in straight vessels. We show that vessel tortuosity causes the CFL to become more asymmetric along the length. We specifically identify a curvature-induced migration of the RBCs as the underlying mechanism of increased asymmetry in curved vessels. The vascular bifurcations and mergers are also seen to change the CFL profiles, and in the majority of them the CFL becomes more asymmetric. For most bifurcations, this is generally observed to occur such that the CFL downstream narrows on the side of the vessel nearest the upstream bifurcation, and widens on the other side. The 3D aspects of such behaviour are elucidated. For many bifurcations, a discrepancy exists between the CFL in the daughter vessels, which arises from a disproportionate partitioning between the flow rate and RBC flux. For most mergers, the downstream CFL narrows in the plane of the merger, but widens away from this plane. The dominant mechanism by which such changes occur is identified as the geometric focusing of the two merging streams. To our knowledge, this work provides the first simulation-based analysis of the 3D CFL structure in complex in vivo-like microvascular networks, including the hydrodynamic origins of the observed behaviour.

Type
JFM Papers
Copyright
© 2019 Cambridge University Press 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Abkarian, M., Lartigue, C. & Viallat, A. 2002 Tank treading and unbinding of deformable vesicles in shear flow: determination of the lift force. Phys. Rev. Lett. 88, 068103.Google Scholar
Balogh, P. & Bagchi, P. 2017a A computational approach to modeling cellular-scale blood flow in complex geometry. J. Comput. Phys. 334, 280307.Google Scholar
Balogh, P. & Bagchi, P. 2017b Direct numerical simulation of cellular-scale blood flow in 3D microvascular networks. Biophys. J. 113, 28152826.Google Scholar
Balogh, P. & Bagchi, P. 2018 Analysis of red blood cell partitioning at bifurcations in simulated microvascular networks. Phys. Fluids 30, 051902.Google Scholar
Barbee, K. 2002 Role of subcellular shear-stress distributions in endothelial cell mechanotransduction. Ann. Biomed. Engng 30, 472482.Google Scholar
Benedict, K., Coffin, G., Barrett, E. & Skalak, T. 2011 Hemodynamic systems analysis of capillary network remodeling during the progression of type 2 diabetes. Microcirculation 18, 6373.Google Scholar
Bloch, E. 1962 A quantitative study of the hemodynamics in the living microvascular system. Am. J. Anat. 110, 125154.Google Scholar
Brust, M., Aouane, O., Thiebaud, M., Flormann, D., Verdier, C., Kaestner, L., Laschke, M., Selmi, H., Benyoussef, A., Podgorski, T., Coupier, G., Misbah, C. & Wagner, C. 2014 The plasma protein fibrinogen stabilizes clusters of red blood cells in microcapillary flows. Sci. Rep. 4, 4348.Google Scholar
Bugliarello, G. & Sevilla, J. 1970 Velocity distribution and other characteristics of steady and pulsatile blood flow in fine glass tubes. Biorheology 7, 85701.Google Scholar
Cantat, I. & Misbah, C. 1999 Lift force and dynamical unbinding of adhering vesicles under shear flow. Phys. Rev. Lett. 83, 880883.Google Scholar
Cassot, F., Lauwers, F., Fouard, C., Prohaska, S. & Lauwers-Cances, V. 2006 A novel three dimensional computer-assisted method for a quantitative study of microvascular networks of the human cerebral cortex. Microcirculation 13, 118.Google Scholar
Chadwick, R. 1985 Slow viscous flow inside a torus – the resistance of small tortuous blood vessels. Q. Appl. Maths 43, 317323.Google Scholar
Copley, A. & Staple, P. 1962 Haemorheological studies on the plasmatic zone in the microcirculation of the cheek pouch of Chinese and Syrian hamsters. Biorheology 1, 314.Google Scholar
Crowl, L. & Fogelson, A. 2010 Computational model of whole blood exhibiting lateral platelet motion induced by red blood cells. Intl J. Numer. Meth. Biomed. Engng 26, 471487.Google Scholar
Coupier, G., Kaoui, B., Podgorski, T. & Misbah, C. 2008 Noninertial lateral migration of vesicles in bounded Poiseuille flow. Phys. Fluids 20, 111702.Google Scholar
Davies, P. & Tripathi, S. 1993 Mechanical stress mechanisms and the cell: an endothelial paradigm. Circulat. Res. 72, 239245.Google Scholar
Enden, G. & Popel, A. 1994 A numerical study of plasma skimming in small vascular bifurcations. Trans. ASME J. Biomech. Engng 116, 7988.Google Scholar
Faivre, M., Abkarian, M., Bickraj, K. & Stone, H. 2006 Geometrical focusing of cells in a microfluidic device: an approach to separate blood plasma. Biorheology 43, 147159.Google Scholar
Fedosov, D., Caswell, B., Popel, A. & Karniadakis, G. 2010 Blood flow and cell-free layer in microvessels. Microcirculation 17, 615628.Google Scholar
Fedosov, D. & Gompper, G. 2014 White blood cell margination in microcirculation. Soft Matt. 10, 29612970.Google Scholar
Fenton, B., Carr, R. & Cokelet, G. 1985 Nonuniform red cell distribution in 20 to 100 μm bifurcations. Microvasc. Res. 29, 103126.Google Scholar
Freund, J. 2007 Leukocyte margination in a model microvessel. Phys. Fluids 19, 023301.Google Scholar
Fung, Y. C. 1993 Biomechanics: Mechanical Properties of Living Tissues, 2nd edn. Springer.Google Scholar
Fung, Y. C. 1996 Biomechanics: Circulation, 2nd edn. Springer.Google Scholar
Grandchamp, X., Coupier, G., Srivastav, A., Minetti, C. & Podgorski, T. 2013 Lift and down-gradient shear-induced diffusion in red blood cell suspensions. Phys. Rev. Lett. 110, 108101.Google Scholar
Katanov, D., Gompper, G. & Fedosov, D. 2015 Microvascular blood flow resistance: role of red blood cell migration and dispersion. Microvasc. Res. 99, 5766.Google Scholar
Kim, S., Kong, R., Popel, A., Intaglietta, M. & Johnson, P. 2006 A computer-based method for determination of the cell-free layer width in microcirculation. Microcirculation 13, 199207.Google Scholar
Kim, S., Kong, R., Popel, A., Intaglietta, M. & Johnson, P. 2007 Temporal and spatial variations of cell-free layer width in arterioles. Am. J. Physiol. Heart Circ. Physiol. 293, H1526H1535.Google Scholar
Kim, S., Ong, P. & Johnson, P. 2009a Effect of dextran 500 on radial migration of erythrocytes in postcapillary venules at low flow rates. Mol. Cell. Biomech. 6 (2), 8391.Google Scholar
Kim, S., Ong, P., Yalcin, O., Intaglietta, M. & Johnson, P. 2009b The cell-free layer in microvascular blood flow. Biorheology 46, 181189.Google Scholar
Koutsiaris, A., Tachmitzi, S., Batis, N., Kotoula, M., Karabatsas, C., Tsironi, E. & Chatzoulis, D. 2007 Volume flow and wall shear stress quantification in the human conjunctival capillaries and post-capillary venules in vivo . Biorheology 44, 375386.Google Scholar
Kumar, A. & Graham, M. 2012 Mechanism of margination in confined flows of blood and other multicomponent suspensions. Phys. Rev. Lett. 109, 108102.Google Scholar
Kruger, T. 2016 Effect of tube diameter and capillary number on platelet margination and near-wall dynamics. Rheol. Acta. 55, 511521.Google Scholar
Leighton, D. & Acrivos, A. 1987 Measurement of shear-induced self-diffusions in concentrated suspensions of spheres. J. Fluid Mech. 177, 109131.Google Scholar
Liao, J., Hein, T., Vaughn, M., Huang, K. & Kuo, L. 1999 Intravascular flow decreases erythrocyte consumption of nitric oxide. Proc. Natl Acad. Sci. USA 96, 87578761.Google Scholar
Lipowsky, H., Kovalcheck, S. & Zweifach, B. 1978 The distribution of blood rheological parameters in the microvasculature of cat mesentery. Circulat. Res. 43, 738749.Google Scholar
Maeda, N., Suzuki, Y., Tanaka, J. & Tateishi, N. 1996 Erythrocyte flow and elasticity of microvessels evaluated by marginal cell-free layer and flow resistance. Am. J. Phys. 271, H2454H2461.Google Scholar
Murata, S., Miyake, Y. & Inaba, T. 1976 Laminar flow in a curved pipe with varying curvature. J. Fluid Mech. 73, 735752.Google Scholar
Namgung, B. & Kim, S. 2014 Effect of uneven red cell influx on formation of cell-free layer in small venules. Microvasc. Res. 92, 1924.Google Scholar
Namgung, B., Ong, P., Johnson, P. & Kim, S. 2011 Effect of cell-free layer variation on arteriolar wall shear stress. Ann. Biomed. Engng 39, 359366.Google Scholar
Ng, Y., Namgung, B., Tien, S., Leo, H. & Kim, S. 2016 Symmetry recovery of cell-free layer after bifurcations of small arterioles in reduced flow conditions: effect of RBC aggregation. Am. J. Physiol. Heart Circ. Physiol. 311, H487H497.Google Scholar
Ong, P., Jain, S. & Kim, S. 2012 Spatio-temporal variations in cell-free layer formation near bifurcations of small arterioles. Microvasc. Res. 83, 118125.Google Scholar
Ong, P., Jain, S., Namgung, B., Woo, Y., Sakai, H., Lim, D., Chun, K. & Kim, S. 2011 An automated method for cell-free layer width determination in small arterioles. Physiol. Meas. 32, N1N12.Google Scholar
Ong, P., Namgung, B., Johnson, P. & Kim, S. 2010 Effect of erythrocyte aggregation and flow rate on cell-free layer formation in arterioles. Am. J. Physiol. Heart Circ. Physiol. 298, H1870H1878.Google Scholar
Oulaid, O. & Zhang, J. 2015 Cell-free layer development process in the entrance region of microvessels. Biomech. Model. Mechanobiol. 14, 783794.Google Scholar
Perkkio, J. & Keskinen, R. 1983 Hematocrit reducing in bifurcations due to plasma skimming. Bull. Math. Biol. 45, 4150.Google Scholar
Pries, A., Ley, K., Claassen, M. & Gaehtgens, P. 1989 Red cell distribution at microvascular bifurcations. Microvasc. Res. 83, 81101.Google Scholar
Pries, A., Secomb, T. & Gaehtgens, P. 1996 Biophysical aspects of blood flow in the microvasculature. Cardiovasc. Res. 32, 654667.Google Scholar
Pozrikidis, C. 2003 Modeling and Simulation of Capsules and Biological Cells, 1st edn. Chapman and Hall/CRC.Google Scholar
Rees, D., Palmer, R. & Moncada, S. 1989 Role of endothelium-derived nitric oxide in the regulation of blood pressure. Proc. Natl Acad. Sci. USA 86, 33753378.Google Scholar
Reinke, W., Gaehtgens, P. & Johnson, P. 1987 Blood viscosity in small tubes: effect of shear rate, aggregation, and sedimentation. Am. J. Phys. 253, H540H547.Google Scholar
Secomb, T. & Pries, A. 2013 Blood viscosity in microvessels: experiment and theory. C. R. Phys. 14, 470478.Google Scholar
Secomb, T. 2017 Blood flow in the microcirculation. Annu. Rev. Fluid Mech. 49, 443461.Google Scholar
Sharan, M. & Popel, A. 2001 A two-phase model for flow of blood in narrow tubes with increased effective viscosity near the wall. Biorheology 38, 415428.Google Scholar
Singh, R., Li, X. & Sarkar, K. 2014 Lateral migration of a capsule in plane shear near a wall. J. Fluid Mech. 739, 421443.Google Scholar
Skalak, R., Tozeren, A., Zarda, P. & Chien, S. 1973 Strain energy function of red blood cell membranes. Biophys. J. 13, 245264.Google Scholar
Smiesko, V. & Johnson, P. 1993 The arterial lumen is controlled by flow-related shear stress. News Physiol. Sci. 8, 3438.Google Scholar
Soutani, M., Suzuki, Y., Tateishi, N. & Maeda, N. 1995 Quantitative evaluation of flow dynamics of erythrocytes in microvessels: influence of erythrocyte aggregation. Am. J. Phys. 268, H1959H1965.Google Scholar
Tateishi, N., Suzuki, Y., Soutani, M. & Maeda, N. 1994 Flow dynamics of erythrocytes in microvessels of isolated rabbit mesentery: cell-free layer and flow resistance. J. Biomech. 27, 11191125.Google Scholar
Verkaik, A., Beulen, B., Bogaerds, A., Rutten, M. & van de Vosse, F. 2009 Estimation of volume flow in curved tubes based on analytical and computational analysis of axial velocity profiles. Phys. Fluids 21, 023602.Google Scholar
Wang, C. & Bassingthwaighte, J. 2003 Blood flow in small curved tubes. Trans. ASME J. Biomech. Engng 125, 910913.Google Scholar
Yan, Z., Acrivos, A. & Weinbaum, S. 1991 Fluid skimming and particle entrainment into a small circular side pore. J. Fluid. Mech. 229, 127.Google Scholar
Ye, S., Ju, M. & Kim, S. 2016 Recovery of cell-free layer and wall shear stress profile symmetry downstream of an arteriolar bifurcation. Microvasc. Res. 106, 1423.Google Scholar
Yin, X. & Zhang, J. 2012 Cell-free layer and wall shear stress variation in microvessels. Biorheol. 49, 261270.Google Scholar
Yin, X., Thomas, T. & Zhang, J. 2013 Multiple red blood cell flows through microvascular bifurcations: cell free layer, cell trajectory, and hematocrit separation. Microvasc. Res. 89, 4756.Google Scholar
Zakrzewicz, A., Secomb, T. & Pries, A. 2002 Angioadaptation: keeping the vascular system in shape. Physiology 17, 197201.Google Scholar
Zhao, H., Shaqfeh, E. & Narsimhan, V. 2012 Shear-induced particle migration and margination in a cellular suspension. Phys. Fluids 24, 011902.Google Scholar
Zong-can, O. & Helfrich, W. 1989 Bending energy of vesicle membranes: general expressions for the first, second, and third variation of the shape energy and applications to spheres and cylinders. Phys. Rev. A 39, 52805288.Google Scholar
Supplementary material: File

Balogh and Bagchi supplementary material

Balogh and Bagchi supplementary material 1

Download Balogh and Bagchi supplementary material(File)
File 739.7 KB