Multiscale modeling of transport and receptor-mediated adhesion of platelets in the bloodstream
Platelet blood cells are microscopic oblate spheroid-shaped particles whose transport and hemostatic functions are strongly affected by the hemodynamic flow environment. A platelet adhesive dynamics (PAD) computational algorithm has been developed to examine the platelet motion and adhesion near a vessel wall at an unprecedented level of spatial and temporal resolution. The numerical model integrates the three-dimensional hydrodynamics of multiple nonspherical cell motion near a wall with the dynamics of receptor-ligand binding. Simulations reveal that a platelet-shaped cell exhibits three distinct types of motion near a wall. Random Brownian motion is found to play a negligible role in the platelet motion, platelet-surface contact frequency and dissociative binding at physiological shear rates. Particle size and proximity of a boundary strongly influence particle collision trajectories, collision times, surface contact areas, and collision frequencies. Computational modeling of platelet aggregation via GPIbα-vWF-GPIbα bond bridges demonstrates the important effects of vWF multimer size, governing receptor-ligand binding kinetics, and nature of cell-cell collisions on the extent of the initial shearinduced thrombus formation. Inter-platelet bond force loading is predicted to be complex and highly nonlinear. The multiscale model is, to date, the most advanced and powerful predictive tool developed for elucidating platelet motion and adhesive phenomena near the vascular wall.