SPECIFIC SYNERGY OF MULTIPLE SUBSTRATE-RECEPTOR INTERACTIONS IN PLATELET THROMBUS FORMATION UNDER FLOW

We have used confocal videomicroscopy in real time to delineate the ad hesive interactions supporting platelet thrombus formation on biologic ally relevant surfaces. Type I collagen fibrils exposed to flowing blo od adsorb von Willebrand factor (VWF), to which platelets become initi ally tethered with continuous surface translocation mediated by the me mbrane glycoprotein Ib alpha. This step is essential at high wall shea r rates to allow subsequent irreversible adhesion and thrombus growth mediated by the integrins alpha(2)beta(1) and alpha(IIb)beta(3). On su bendothelial matrix, endogenous vWF and adsorbed plasma vWF synergisti cally initiate platelet recruitment, and alpha(2)beta(1) remains key a long with alpha(IIb)beta(3) for normal thrombus development at all but low shear rates. Thus, hemodynamic forces and substrate characteristi cs define the platelet adhesion pathways leading to thrombogenesis.