A multiscale biomechanical model of platelets: Correlating with in-vitro results

Abstract

Using dissipative particle dynamics (DPD) combined with coarse grained molecular dynamics (CGMD) approaches, we developed a multiscale deformable platelet model to accurately describe the molecular-scale intra-platelet constituents and biomechanical properties of platelets in blood flow. Our model includes the platelet bilayer membrane, cytoplasm and an elaborate elastic cytoskeleton. Correlating numerical simulations with published in-vitro experiments, we validated the biorheology of the cytoplasm, the elastic response of membrane to external stresses, and the stiffness of the cytoskeleton actin filaments, resulting in an accurate representation of the molecular-level biomechanical microstructures of platelets. This enabled us to study the mechanotransduction process of the hemodynamic stresses acting onto the platelet membrane and transmitted to these intracellular constituents. The platelets constituents continuously deform in response to the flow induced stresses. To the best of our knowledge, this is the first molecular-scale platelet model that can be used to accurately predict platelets activation mechanism leading to thrombus formation in prosthetic cardiovascular devices and in vascular disease processes. This model can be further employed to study the effects of novel therapeutic approaches of modulating platelet properties to enhance their shear resistance via mechanotransduction pathways.

Keywords: Biomechanical; Mechanotransduction; Multiscale modeling; Platelets; Thrombosis.