Computational investigation of platelet adhesion mediated by von Willebrand factor under shear flow

Abstract

von Willebrand factor (vWF) is a crucial plasma glycoprotein that facilitates thrombus formation by promoting platelet recruitment in response to shear-induced conformational changes during blood flow, particularly under high-shear stress conditions. Despite its recognized thrombogenic role, the behavior of vWF chains in complex flow environments has not been fully characterized. This study utilized detailed mesoscopic simulations based on dissipative particle dynamics to investigate interactions among blood cells, blood plasma, and functionalized vessel surfaces. Significant transitions of vWF chains from a globule state to an extended conformation were revealed with increasing shear rates, elucidating their critical role in platelet recruitment and adhesion dynamics. The extent of vWF chain stretching was quantified via mean square end-to-end distance analysis, confirming its sensitivity to applied shear rates. Mechanisms of platelet adhesion on fibrinogen- and vWF-coated surfaces were examined, with fibrinogen exhibiting effectively platelet binding at low shear rates (less than 600s) while vWF displayed a strong affinity for platelets at high-shear rates exceeding 1000s. A systematic analysis of the influence of vWF chain length and density on platelet adhesion were conducted, resulting in the development of a novel phase diagram categorizing three distinct adhesion regimes. The distinctive role of vWF chains in vaso-occlusive crises at elevated shear rates was further investigated, highlighting the importance of varying blood flow velocities in both physiological and pathological contexts. Collectively, these results provide valuable insight into vWF-mediated platelet adhesion under various shear flow conditions, thereby enhancing the understanding of the early stages of thrombus formation.