Application of Multiphase Computational Fluid Dynamics to Analyze Monocyte Adhesion

Study of the mechanisms of monocyte adhesion initiating atheroslerotic lesions has engaged investigators for decades. Single-phase computational fluid dynamics (CFD) analyses fail to account for particulate migration. Consequently, inconsistencies arise when correlating adhesion with wall shear stress (WSS). The purpose of this paper is to present, to our knowledge, the first computational analysis of in vitro U937 monocyte-like human cell adhesion data using a coupled multiphase CFD-population balance adhesion model. The CFD model incorporates multiphase non-Newtonian hemodynamic models to compute the spatial distributions of freely flowing monocytes and WSSs in control volumes adjacent to the wall. Measurements of monocyte adhesion onto an E-selectin-coated flow model that included an idealized stenosis and an abrupt expansion were available from the literature. In this study, we develop a new monolayer population balance adhesion model, based on the widely accepted mechanism of ligand–receptor binding, coupled to the CFD results. The monolayer population balance model accounts for the interactions of freely flowing, rolling, and adhering monocytes with surfaces via first-order reactions, transport of rolling cells in the monolayer, and the concept of a WSS detachment threshold, clearly evident in the adhesion experiments. The new paradigm of coupling the multiphase hemodynamic CFD model with the proposed adhesion model is illustrated by determining and interpreting the model parameters for experimental datasets having Reynolds numbers of 100 and 140. The coupled multiphase CFD adhesion model is able to simultaneously predict the spatial variations in freely flowing monocytes, their adherent number density, and carrier fluid WSSs adjacent to ligand-coated flow cell surfaces.

[1]  D. Hammer,et al.  The state diagram for cell adhesion under flow: leukocyte rolling and firm adhesion. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[2]  R L Kormos,et al.  Hemodynamics and the vascular endothelial cytoskeleton , 1987, The Journal of cell biology.

[3]  G. T. Polley,et al.  TEN YEARS OF EBERT, PANCHAL AND THE ‘THRESHOLD FOULING’ CONCEPT , 2005 .

[4]  R M Nerem,et al.  Hemodynamics and the vascular endothelium. , 1993, Journal of biomechanical engineering.

[5]  C Kleinstreuer,et al.  A focal stress gradient-dependent mass transfer mechanism for atherogenesis in branching arteries. , 1996, Medical engineering & physics.

[6]  S. Alper,et al.  Hemodynamic shear stress and its role in atherosclerosis. , 1999, JAMA.

[7]  D. Giddens,et al.  Effects of wall shear stress and fluid recirculation on the localization of circulating monocytes in a three-dimensional flow model. , 1995, Journal of biomechanics.

[8]  Robert W. Lyczkowski,et al.  State-of-the-art review of erosion modeling in fluid/solids systems , 2002 .

[9]  A. Barakat,et al.  Spatial relationships in early signaling events of flow-mediated endothelial mechanotransduction. , 1997, Annual review of physiology.

[10]  A. Fischer Leukocyte adhesion. , 1993, Clinical and experimental rheumatology.

[11]  C. B. Panchal,et al.  Analysis of Exxon crude-oil-slip stream coking data , 1995 .

[12]  Evan Evans,et al.  Nano-to-micro scale dynamics of P-selectin detachment from leukocyte interfaces. III. Numerical simulation of tethering under flow. , 2005, Biophysical journal.

[13]  Ahmed Hassanein,et al.  Multiphase hemodynamic simulation of pulsatile flow in a coronary artery. , 2006, Journal of biomechanics.

[14]  J. Marshall,et al.  Micro-scale Dynamic Simulation of Erythrocyte–Platelet Interaction in Blood Flow , 2008, Annals of Biomedical Engineering.

[15]  D. Ku,et al.  Fluid mechanics of vascular systems, diseases, and thrombosis. , 1999, Annual review of biomedical engineering.

[16]  R K Jain,et al.  Role of erythrocytes in leukocyte-endothelial interactions: mathematical model and experimental validation. , 1996, Biophysical journal.

[17]  N. Depaola,et al.  Flow-conditioned HUVECs support clustered leukocyte adhesion by coexpressing ICAM-1 and E-selectin. , 2005, American journal of physiology. Heart and circulatory physiology.

[18]  John A. Frangos,et al.  Temporal Gradients in Shear, but Not Spatial Gradients, Stimulate Endothelial Cell Proliferation , 2001, Circulation.

[19]  R. Schroter,et al.  Arterial Wall Shear and Distribution of Early Atheroma in Man , 1969, Nature.

[20]  Ahmed Hassanein,et al.  Hemodynamic Computation Using Multiphase Flow Dynamics in a Right Coronary Artery , 2006, Annals of Biomedical Engineering.

[21]  P. Worth Longest,et al.  Efficient computation of micro-particle dynamics including wall effects , 2004 .

[22]  Chih-Ming Ho,et al.  Monocyte recruitment to endothelial cells in response to oscillatory shear stress , 2003, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[23]  E L Berg,et al.  A direct comparison of selectin-mediated transient, adhesive events using high temporal resolution. , 1999, Biophysical journal.

[24]  Aaron L. Fogelson,et al.  Computational Methods for Continuum Models of Platelet Aggregation , 1999 .

[25]  Jizhong Lou,et al.  Mechanisms for Flow-Enhanced Cell Adhesion , 2008, Annals of Biomedical Engineering.

[26]  D. Hammer,et al.  Cell-free rolling mediated by L-selectin and sialyl Lewis(x) reveals the shear threshold effect. , 2000, Biophysical journal.

[27]  Sriram Neelamegham,et al.  An analysis tool to quantify the efficiency of cell tethering and firm-adhesion in the parallel-plate flow chamber. , 2003, Journal of immunological methods.

[28]  Timothy A. Springer,et al.  The Kinetics of L-selectin Tethers and the Mechanics of Selectin-mediated Rolling , 1997, The Journal of cell biology.

[29]  V. Moy,et al.  Molecular basis for the dynamic strength of the integrin alpha4beta1/VCAM-1 interaction. , 2004, Biophysical journal.

[30]  G. Truskey,et al.  Characterization of a sudden expansion flow chamber to study the response of endothelium to flow recirculation. , 1995, Journal of biomechanical engineering.

[31]  D. Lauffenburger,et al.  Molecular properties in cell adhesion: a physical and engineering perspective. , 2001, Trends in biotechnology.

[32]  C. Zhu,et al.  Kinetics and mechanics of cell adhesion. , 2000, Journal of biomechanics.

[33]  M. Thubrikar,et al.  Pressure-induced arterial wall stress and atherosclerosis. , 1995, The Annals of thoracic surgery.

[34]  G. I. Bell Models for the specific adhesion of cells to cells. , 1978, Science.

[35]  S. Neelamegham,et al.  Estimation of cell capture and arrest efficiency in flow chambers , 2002, Proceedings of the Second Joint 24th Annual Conference and the Annual Fall Meeting of the Biomedical Engineering Society] [Engineering in Medicine and Biology.

[36]  P. Walker,et al.  Disturbed flow promotes deposition of leucocytes from flowing whole blood in a model of a damaged vessel wall , 2004, British journal of haematology.

[37]  David A. Steinman,et al.  Flow Imaging and Computing: Large Artery Hemodynamics , 2005, Annals of Biomedical Engineering.

[38]  R K Jain,et al.  Analysis of cell flux in the parallel plate flow chamber: implications for cell capture studies. , 1994, Biophysical journal.

[39]  Daniel A. Hammer,et al.  Simulation of cell rolling and adhesion on surfaces in shear flow , 1991, Cell Biophysics.

[40]  P. Walker,et al.  Population of the Vessel Wall by Leukocytes Binding to P-Selectin in a Model of Disturbed Arterial Flow , 2001, Arteriosclerosis, thrombosis, and vascular biology.

[41]  D. Gidaspow Multiphase Flow and Fluidization: Continuum and Kinetic Theory Descriptions , 1994 .

[42]  J. Frangos,et al.  Mechanism of temporal gradients in shear-induced ERK1/2 activation and proliferation in endothelial cells. , 2001, American journal of physiology. Heart and circulatory physiology.

[43]  Charles Taylor,et al.  EXPERIMENTAL AND COMPUTATIONAL METHODS IN CARDIOVASCULAR FLUID MECHANICS , 2004 .

[44]  Clement Kleinstreuer,et al.  Comparison of blood particle deposition models for non-parallel flow domains. , 2003, Journal of biomechanics.

[45]  S. L. Vasin,et al.  Mathematical model of static platelet adhesion on a solid surface. , 2003, Journal of biomedical materials research. Part A.

[46]  W. Erl,et al.  Adhesion properties of Mono Mac 6, a monocytic cell line with characteristics of mature human monocytes. , 1995, Atherosclerosis.

[47]  Wei Shyy,et al.  Moving boundaries in micro-scale biofluid dynamics , 2001 .

[48]  D. Lauffenburger,et al.  A dynamical model for receptor-mediated cell adhesion to surfaces. , 1987, Biophysical journal.

[49]  R. Henderson,et al.  Three-dimensional instability in flow over a backward-facing step , 2000, Journal of Fluid Mechanics.

[50]  J A Frangos,et al.  Analysis of temporal shear stress gradients during the onset phase of flow over a backward-facing step. , 2001, Journal of biomechanical engineering.

[51]  D. Hammer,et al.  Adhesive dynamics simulations of sialyl-Lewis(x)/E-selectin-mediated rolling in a cell-free system. , 2000, Biophysical journal.

[52]  Sriram Neelamegham,et al.  PPLATE: a computer program for analysis of parallel-plate flow chamber experimental data. , 2003, Journal of immunological methods.

[53]  Larry V. McIntire,et al.  Effect of flow on polymorphonuclear leukocyte/endothelial cell adhesion , 1987 .

[54]  David A. Steinman,et al.  Image-Based Computational Fluid Dynamics Modeling in Realistic Arterial Geometries , 2002, Annals of Biomedical Engineering.

[55]  D. Giddens,et al.  Local hemodynamics affect monocytic cell adhesion to a three-dimensional flow model coated with E-selectin. , 2001, Journal of biomechanics.

[56]  M. Kluger,et al.  Vascular endothelial cell adhesion and signaling during leukocyte recruitment. , 2004, Advances in dermatology.

[57]  T David,et al.  Platelet deposition in stagnation point flow: an analytical and computational simulation. , 2001, Medical engineering & physics.

[58]  Vincent T. Moy,et al.  Molecular Basis for the Dynamic Strength of the Integrin α4β1/VCAM-1 Interaction , 2004 .

[59]  M. Gimbrone,et al.  Vascular endothelium responds to fluid shear stress gradients. , 1992, Arteriosclerosis and thrombosis : a journal of vascular biology.

[60]  N Harbeck,et al.  Spatial and temporal regulation of gap junction connexin43 in vascular endothelial cells exposed to controlled disturbed flows in vitro. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[61]  Rakesh K Jain,et al.  Red blood cells augment leukocyte rolling in a virtual blood vessel. , 2002, Biophysical journal.

[62]  B. Armaly,et al.  Experimental and theoretical investigation of backward-facing step flow , 1983, Journal of Fluid Mechanics.

[63]  Michael M. Resch,et al.  Pulsatile non-Newtonian flow characteristics in a three-dimensional human carotid bifurcation model. , 1991, Journal of biomechanical engineering.

[64]  C F Dewey,et al.  Shear stress gradients remodel endothelial monolayers in vitro via a cell proliferation-migration-loss cycle. , 1997, Arteriosclerosis, thrombosis, and vascular biology.

[65]  B. K. Lok,et al.  Protein adsorption on crosslinked polydimethylsiloxane using total internal reflection fluorescence , 1983 .

[66]  D. J. Goetz,et al.  Leukocyte adhesion: an exquisite balance of hydrodynamic and molecular forces. , 2003, News in physiological sciences : an international journal of physiology produced jointly by the International Union of Physiological Sciences and the American Physiological Society.

[67]  C Ross Ethier,et al.  The relationship between wall shear stress distributions and intimal thickening in the human abdominal aorta , 2003, Biomedical engineering online.

[68]  K. Ley,et al.  Adhesion molecules and atherogenesis. , 2001, Acta physiologica Scandinavica.

[69]  P. Davies Endothelial Transcriptome Profiles In Vivo in Complex Arterial Flow Fields , 2008, Annals of Biomedical Engineering.