3D computational modeling and simulation of leukocyte rolling adhesion and deformation. 2008

Vijay Pappu, and Prosenjit Bagchi
Department of Mechanical and Aerospace Engineering, Rutgers University, The State University of New Jersey, 98 Brett Road, Piscataway, NJ 08854, USA.

A 3D computational fluid dynamic (CFD) model is presented to simulate transient rolling adhesion and deformation of leukocytes over a P-selectin coated surface in shear flow. The computational model is based on immersed boundary method for cell deformation, and stochastic Monte Carlo simulation for receptor/ligand interaction. The model is shown to predict the characteristic 'stop-and-go' motion of rolling leukocytes. Here we examine the effect of cell deformation, shear rate, and microvilli distribution on the rolling characteristics. Comparison with experimental measurements is presented throughout the article. We observe that compliant cells roll more stably, and have longer pause times due to reduced bond force and increased bond lifetime. Microvilli presentation is shown to affect rolling characteristics by altering the step size, but not pause times. Our simulations predict a significant sideway motion of the cell arising purely due to receptor/ligand interaction, and discrete nature of microvilli distribution. Adhesion is seen to occur via multiple tethers, each of which forms multiple selectin bonds, but often one tether is sufficient to support rolling. The adhesion force is concentrated in only 1-3 tethered microvilli in the rear-most part of a cell. We also observe that the number of selectin bonds that hold the cell effectively against hydrodynamic shear is significantly less than the total adhesion bonds formed between a cell and the substrate. The force loading on individual microvillus and selectin bond is not continuous, rather occurs in steps. Further, we find that the peak force on a tethered microvillus is much higher than that measured to cause tether extrusion.

UI MeSH Term Description Entries
D008871 Microvilli Minute projections of cell membranes which greatly increase the surface area of the cell. Brush Border,Striated Border,Border, Brush,Border, Striated,Borders, Brush,Borders, Striated,Brush Borders,Microvillus,Striated Borders
D008954 Models, Biological Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment. Biological Model,Biological Models,Model, Biological,Models, Biologic,Biologic Model,Biologic Models,Model, Biologic
D002448 Cell Adhesion Adherence of cells to surfaces or to other cells. Adhesion, Cell,Adhesions, Cell,Cell Adhesions
D003198 Computer Simulation Computer-based representation of physical systems and phenomena such as chemical processes. Computational Modeling,Computational Modelling,Computer Models,In silico Modeling,In silico Models,In silico Simulation,Models, Computer,Computerized Models,Computer Model,Computer Simulations,Computerized Model,In silico Model,Model, Computer,Model, Computerized,Model, In silico,Modeling, Computational,Modeling, In silico,Modelling, Computational,Simulation, Computer,Simulation, In silico,Simulations, Computer
D004548 Elasticity Resistance and recovery from distortion of shape.
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D001698 Biomedical Engineering Application of principles and practices of engineering science to biomedical research and health care. Clinical Engineering,Engineering, Clinical,Engineering, Biomedical
D012212 Rheology The study of the deformation and flow of matter, usually liquids or fluids, and of the plastic flow of solids. The concept covers consistency, dilatancy, liquefaction, resistance to flow, shearing, thixotrophy, and VISCOSITY. Flowmetry,Velocimetry,Velocimetries
D021621 Imaging, Three-Dimensional The process of generating three-dimensional images by electronic, photographic, or other methods. For example, three-dimensional images can be generated by assembling multiple tomographic images with the aid of a computer, while photographic 3-D images (HOLOGRAPHY) can be made by exposing film to the interference pattern created when two laser light sources shine on an object. Computer-Assisted Three-Dimensional Imaging,Imaging, Three-Dimensional, Computer Assisted,3-D Image,3-D Imaging,Computer-Generated 3D Imaging,Three-Dimensional Image,Three-Dimensional Imaging, Computer Generated,3 D Image,3 D Imaging,3-D Images,3-D Imagings,3D Imaging, Computer-Generated,3D Imagings, Computer-Generated,Computer Assisted Three Dimensional Imaging,Computer Generated 3D Imaging,Computer-Assisted Three-Dimensional Imagings,Computer-Generated 3D Imagings,Image, 3-D,Image, Three-Dimensional,Images, 3-D,Images, Three-Dimensional,Imaging, 3-D,Imaging, Computer-Assisted Three-Dimensional,Imaging, Computer-Generated 3D,Imaging, Three Dimensional,Imagings, 3-D,Imagings, Computer-Assisted Three-Dimensional,Imagings, Computer-Generated 3D,Imagings, Three-Dimensional,Three Dimensional Image,Three Dimensional Imaging, Computer Generated,Three-Dimensional Images,Three-Dimensional Imaging,Three-Dimensional Imaging, Computer-Assisted,Three-Dimensional Imagings,Three-Dimensional Imagings, Computer-Assisted
D036904 Leukocyte Rolling Movement of tethered, spherical LEUKOCYTES along the endothelial surface of the microvasculature. The tethering and rolling involves interaction with SELECTINS and other adhesion molecules in both the ENDOTHELIUM and leukocyte. The rolling leukocyte then becomes activated by CHEMOKINES, flattens out, and firmly adheres to the endothelial surface in preparation for transmigration through the interendothelial cell junction. (From Abbas, Cellular and Molecular Immunology, 3rd ed) Leucocyte Rolling,Rolling, Leucocyte,Rolling, Leukocyte

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