Supercomputer simulations of platelet activation in blood plasma at multiple scales

Thrombogenicity in cardiovascular devices and pathologies is associated with flow-induced shear stress activation of platelets resulting from pathological flow patterns. This platelet activation process poses a major modeling challenge as it covers disparate spatiotemporal scales, from flow down to cellular, to subcellular, and to molecular scales. This challenge can be resolved by implementing multiscale simulations feasible only on supercomputers. The simulation must couple the macroscopic effects of blood plasma flow and stresses to a microscopic platelet dynamics. In an attempt to model this complex and multiscale behavior we have first developed a phenomenological three-dimensional coarse-grained molecular dynamics (CGMD) particle-based model. This model depicts resting platelets and simulates their characteristic filopodia formation observed during activation. Simulations results are compared with in vitro measurements of activated platelet morphological changes, such as the core axes and filopodia thicknesses and lengths, after exposure to the prescribed flow-induced shear stresses. More recently, we extended this model by incorporating the platelet in Dissipative Particle Dynamics (DPD) blood plasma flow and developed a dynamic coupling scheme that allows the simulation of flow-induced shear stress platelet activation. This portion of research is in progress.