Shear-regulated platelet translocation and aggregation in heterogeneous arterial microflows: A three-dimensional transport–reaction model

Arterial thrombosis is driven by shear-dependent platelet adhesion in which fast, transient glycoprotein Ibα (GPIbα)–von Willebrand factor (VWF) bonds initiate capture and rolling, followed by slower αIIbβ3-mediated stabilization via VWF and/or fibrinogen. Because these pathways co-occur with strong spatial shear heterogeneity, their combined contribution to aggregate morphology and growth dynamics remains difficult to quantify. Here, we present a three-dimensional continuum, transport–reaction model that resolves coupled hemodynamics, platelet advection–diffusion, and mechanosensitive surface kinetics for free-flowing, translocating (rolling), and irreversibly incorporated platelets. The evolving aggregate is represented as a permeable volume, enabling two-way feedback between growth-induced flow disturbance and platelet transport. Model parameters are calibrated and validated against microfluidic measurements at arterial wall shear rates (WSRs) of 800 and 4000 s−1, reproducing distinct shear-regulated growth regimes and morphologies. Using the finite-element method, the resulting computational model is then applied to two pathologic flow configurations: a stenotic microchannel that produces occlusive, high-shear aggregation and a block-post geometry representative of blood-contacting devices with sharp shear gradients. Simulations show that early platelet translocation, combined with co-acting, in vitro-calibrated binding kinetics, captures experimentally observed growth dynamics and three-dimensional morphology in both geometries. The porous aggregate representation is critical for accurate prediction of near-surface platelet fluxes and downstream transport. Finally, the model indicates that the translocating platelet layer acts as a transport corridor that enhances distal platelet availability, promotes lateral spreading, and facilitates coalescence of neighboring aggregates. Together, this study establishes a computational model for the investigation of the early stages of arterial thrombus formation under heterogeneous arterial microflows.