Computational modeling of dynamic cell adhesion, deformation, and rolling under blood flow in a microchannel

Cell adhesion to postcapillary vascular endothelium in the fluid dynamic environment is an important aspect of many physiological and pathological processes. One of the most fascinating adhesions in nature is the dynamic binding of leukocytes with the wall of blood vessels during immune responses where the cell exits from the blood vessel and enters the infected tissue. The effects of the hemodynamics on cell adhesion in steadystate are well established, although the detailed mechanisms of the adhesion under dynamic conditions remain elusive. Thus, an understanding of this dynamic process may give clues as to the molecular mechanism of cell adhesion. To elucidate the roles of flow force, adhesion force, and cell deformation in leukocyte rolling under a dynamic blood flow, a computational model combining microscale cell-blood interaction and nanoscale receptor-ligand mediated adhesion kinetics has been developed.; This model investigates the dynamic behavior of cell deformation assuming dynamic ligand-receptor binding and is solved by the finite volume method (FVM). The effects of cell-fluid interactions are modeled using a fluid-structure interaction method. The cell adhesion kinetic model is used to investigate the molecular receptor-ligand binding. The cell is modeled as a deformable elastic solid adhered to the micro-channel wall, which may be acceptable as the cell undergoes small deformation, and blood is simulated using a non-Newtonian blood model. For simplicity, the curvature of microchannei walls is neglected in the current model by assuming a flat surface. The ligand-receptor bonds between cell and the microchannel wall are simulated as simple springs. The different length scales characterizing cell adhesion are resolved separately and linked by using the matching condition between cell-fluid interaction and cell-endothelium adhesion.; It is found that cell adhesion processes are regulated by forces due to the cell-fluid interaction and forces due to the receptor-ligand mediated. Cell deformation has a significant impact on cell adhesion and therefore on the rolling process by dynamically changing its shape. The relationship between transient cell rolling velocity and inlet wall shear stress has been obtained. The simulations demonstrate that the dynamics of receptor-ligand binding under flow is controlled by mechanochemical properties of nanoscale adhesion molecules. We have shown that dynamics of receptor-ligand binding can be understood in terms of reaction rates, adhesion affinity, receptor-ligand bond stiffness, and reactive compliance. The model reveals that the dynamic behaviors are the key features in the cell adhesion processes and static methods may not be able to predict the cell adhesion behaviors accurately.