We developed a multiscale model for simulating aggregation of multiple, free-flowing platelets in low-intermediate shear viscous flow, in which aggregation is mediated by the interaction of αIIbβ3 receptors on the platelet membrane and fibrinogen (Fg). This multiscale model uses coarse grained molecular dynamics (CGMD) for platelets at the microscales and dissipative particle dynamics (DPD) for the shear flow at the macroscales, employing our hybrid aggregation force field for modeling molecular level receptor ligand bonds. We define an aggregation tensor and use it to quantify the molecular level contact characteristics between platelets in an aggregate. We perform numerical studies under different flow conditions for platelet doublets and triplets and evaluate the contact area, detaching force and minimum distance between different pairs of platelets in an aggregate. We also present the dynamics of applied stress and velocity magnitude distributions on the platelet membrane during aggregation and quantify the increase in stress in the contact region under different flow conditions. Integrating the knowledge from our previously validated models, together with new aggregation scenarios, our model can dynamically quantify aggregation characteristics and map stress and velocity distribution on the platelet membrane which are difficult to measure in vitro, thus providing an insight into mechanotransduction bond formation response of platelets to flow-induced shear stresses. This modeling framework, together with the tensor method for quantifying inter-platelet contact, can be extended to simulate and analyze larger aggregates and their adhesive properties.
Keywords: Aggregation tensor; Contact area; Free-flowing aggregation; Multiscale modeling; Stress distribution.