(170d) Deformable Multiparticle Adhesive Dynamics. A New Parallel Computational Method for the Receptor-Mediated Adhesion of Multiple Elastically Deformable Cells near a Wall In Shear Flow

Human immune response triggers a cascade of events that begins with receptor-mediated adhesion of blood cells to the vasculature. Neutrophils typically contain between 28,000-50,000 sialylated carbohydrate ligands to the counter-receptor P-selectin, expressed by endothelial cells. In this simulation, we treat the neutrophil as an elastic solid with a physiologically relevant surface density of adhesion molecules. Tether bond formation to and dissociation from the vascular wall (Bell, 1978) are treated in a stochastic fashion (Hammer and Apte, 1992) and the ensuing traction forces ?¬together with hydrodynamic forces due to an imposed linear shear flow? are used to calculate the cell's translational and rotational motion. The surface traction distribution is also computed in order to calculate the displacement of the cell surface elements. This extension of the Multiparticle Adhesive Dynamics algorithm (MAD, King and Hammer, 2001) to treat deformable cells is a critical step in the evolution of computer models of inflammation. Namely, we may address the question, does cell deformation during rolling stabilize cell rolling velocity in the presence of increased shear rate? Due to increased computational demands of the Deformable Multiparticle Adhesive Dynamics (DMAD) algorithm, a parallel implementation (pDMAD) has been developed in order to speed-up the simulation performance nearly N-fold. The new parallel implementation has been applied to the problem of receptor-mediated adhesion along the vessel wall. With this simulation, we address this stabilization question; but more importantly we are also able to simulate the interaction and collision of hundreds of interacting cells.

1. Bell GI. Models for the specific adhesion of cells to cells. Science 200:618?27, 1978.

2. Hammer DA, SM Apte. Simulation of cell rolling and adhesion on surfaces in shear flow: general results and analysis of selectin-mediated neutrophil adhesion. Biophys. J. 63:35?57, 1992.

3. King MR, DA Hammer. Multiparticle adhesive dynamics: hydrodynamic recruitment of rolling leukocytes. Proc Natl Acad Sci USA 98:14919?24, 2001.

Keywords: leukocyte deformation, receptor-mediated adhesion, boundary integral equation method (BIEM)