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When a blood vessel ruptures or gets inflamed, the human body responds byrapidly forming a clot to restrict the loss of blood. Platelets aggregation atthe injury site of the blood vessel occurring via platelet-platelet adhesion,tethering and rolling on the injured endothelium is a critical initial step inblood clot formation. A novel three-dimensional multiscale model is introducedand used in this paper to simulate receptor-mediated adhesion of deformableplatelets at the site of vascular injury under different shear rates of bloodflow. The novelty of the model is based on a new approach of coupling submodelsat three biological scales crucial for the early clot formation: novel hybridcell membrane submodel to represent physiological elastic properties of aplatelet, stochastic receptor-ligand binding submodel to describe cell adhesionkinetics and Lattice Boltzmann submodel for simulating blood flow. The modelimplementation on the GPUs cluster significantly improved simulationperformance. Predictive model simulations revealed that platelet deformation,interactions between platelets in the vicinity of the vessel wall as well asthe number of functional GPIb{\alpha} platelet receptors played significantroles in the platelet adhesion to the injury site. Variation of the number offunctional GPIb{\alpha} platelet receptors as well as changes of plateletstiffness can represent effects of specific drugs reducing or enhancingplatelet activity. Therefore, predictive simulations can improve the search fornew drug targets and help to make treatment of thrombosis patient specific.

philosophical transactions - royal society. mathematical, physical and engineering sciences/philosophical transactions - royal society. mathematical, physical and engineering sciences

Three-dimensional Multiscale Model of Deformable Platelets Adhesion to Vessel Wall in Blood Flow