We developed a phenomenological three-dimensional (3D) platelet model to characterize the filopodia formation observed during early stage platelet activation. Departing from continuum mechanics based approaches; this coarse-grained molecular dynamics (CGMD) particle-based model can deform to emulate the complex shape change and filopodia formation that platelets undergo during activation. The platelet peripheral zone is modeled with a two-layer homogeneous elastic structure represented by spring-connected particles. The structural zone is represented by a cytoskeletal assembly comprising of a filamentous core and filament bundles supporting the platelet’s discoid shape, also modeled by spring-connected particles. The interior organelle zone is modeled by homogeneous cytoplasm particles that facilitate the platelet deformation. Non-bonded interactions among the discrete particles of the membrane, cytoskeletal assembly, and the cytoplasm are described using the Lennard-Jones potential with empirical constants. By exploring the parameter space of this CGMD model, we have successfully simulated the dynamics of varied filopodia formations. Comparative analyses of length and thickness of filopodia show that our numerical simulations are in agreement with experimental measurements of flow-induced activated platelets.

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The coagulation cascade of blood may be initiated by flow induced platelet activation, which prompts clot formation in prosthetic cardiovascular devices and arterial disease processes. While platelet activation may be induced by biochemical agonists, shear stresses arising from pathological flow patterns enhance the propensity of platelets to activate and initiate the intrinsic pathway of coagulation, leading to thrombosis. Upon activation platelets undergo complex biochemical and morphological changes: organelles are centralized, membrane glycoproteins undergo conformational changes, and adhesive pseudopods are extended. Activated platelets polymerize fibrinogen into a fibrin network that enmeshes red blood cells. Activated platelets also cross-talk and aggregate to form thrombi. Current numerical simulations to model this complex process mostly treat blood as a continuum and solve the Navier-Stokes equations governing blood flow, coupled with diffusion-convection-reaction equations. It requires various complex constitutive relations or simplifying assumptions, and is limited to μm level scales. However, molecular mechanisms governing platelet shape change upon activation and their effect on rheological properties can be in the nm level scales. To address this challenge, a multiscale approach which departs from continuum approaches, may offer an effective means to bridge the gap between macroscopic flow and cellular scales. Coarse Grained Molecular dynamics (CGMD) and discrete/dissipative particle dynamics (DPD) methods have been employed in recent years to simulate complex processes at the molecular scales, and various viscous fluids at low-to-high Reynolds numbers at mesoscopic scales. Such particle methods possess important properties at the mesoscopic scale: complex fluids with heterogeneous particles can be modeled, allowing the simulation of processes which are otherwise very difficult to solve by continuum approaches. It is becoming a powerful tool for simulating complex blood flow, red blood cells interactions, and platelet-mediated thrombosis involving platelet activation, aggregation, and adhesion.