title: Three-dimensional multi-scale model of deformable platelets adhesion to vessel wall in blood flow.
abstract: When a blood vessel ruptures or gets inflamed, the human body responds by rapidly forming a clot to restrict the loss of blood. Platelets aggregation at the injury site of the blood vessel occurring via platelet-platelet adhesion, tethering and rolling on the injured endothelium is a critical initial step in blood clot formation. A novel three-dimensional multi-scale model is introduced and used in this paper to simulate receptor-mediated adhesion of deformable platelets at the site of vascular injury under different shear rates of blood flow. The novelty of the model is based on a new approach of coupling submodels at three biological scales crucial for the early clot formation: novel hybrid cell membrane submodel to represent physiological elastic properties of a platelet, stochastic receptor-ligand binding submodel to describe cell adhesion kinetics and lattice Boltzmann submodel for simulating blood flow. The model implementation on the GPU cluster significantly improved simulation performance. Predictive model simulations revealed that platelet deformation, interactions between platelets in the vicinity of the vessel wall as well as the number of functional GPIbα platelet receptors played significant roles in platelet adhesion to the injury site. Variation of the number of functional GPIbα platelet receptors as well as changes of platelet stiffness can represent effects of specific drugs reducing or enhancing platelet activity. Therefore, predictive simulations can improve the search for new drug targets and help to make treatment of thrombosis patient-specific.
authors: Department of Applied and Computational Mathematics and Statistics, University of Notre Dame, Notre Dame, IN 46556, USA malber@nd.edu.
authors: Ziheng
authors: Z
authors: Wu
authors: Department of Applied and Computational Mathematics and Statistics, University of Notre Dame, Notre Dame, IN 46556, USA.
authors: Zhiliang
authors: Z
authors: Xu
authors: Department of Applied and Computational Mathematics and Statistics, University of Notre Dame, Notre Dame, IN 46556, USA.
authors: Oleg
authors: O
authors: Kim
authors: Department of Applied and Computational Mathematics and Statistics, University of Notre Dame, Notre Dame, IN 46556, USA Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
authors: Mark
authors: M
authors: Alber
mesh_terms: D000818:Animals; D001158:Arteries / Q000473:pathology / Q000503:physiopathology*; D001783:Blood Flow Velocity / Q000502:physiology; D001792:Blood Platelets / Q000473:pathology; D001794:Blood Pressure; D003198:Computer Simulation; D006801:Humans; D008955:Models, Cardiovascular; D015539:Platelet Activation; D010973:Platelet Adhesiveness; D033081:Shear Strength; D057772:Vascular System Injuries / Q000473:pathology / Q000503:physiopathology*
keywords: cell flow interaction; lattice Boltzmann; platelet adhesion; stochastic receptor–ligand model; three-dimensional model; thrombus