Platelet Adhesive Dynamics. Part II: High Shear-Induced Transient Aggregation via GPIb α-vWF-GPIb α Bridging

Abstract

A three-dimensional multiscale computational model, platelet adhesive dynamics (PAD), is developed and applied in Part I and Part II articles to characterize and quantify key biophysical aspects of GPIb α-von-Willebrand-factor (vWF)-mediated interplatelet binding at high shear rates, a necessary and enabling step that initiates shear-induced platelet aggregation. In this article, an adhesive dynamics model of the transient aggregation of two unactivated platelets via GPIb α-vWF-GPIb α bridging is developed and integrated with the three-dimensional hydrodynamic flow model discussed in Part I. Platelet binding efficiencies predicted by PAD are in good agreement with platelet aggregation behavior observed experimentally, as documented in the literature. Deviations from average vWF ligand size or healthy GPIb α-vWF-A1 binding kinetics are observed in simulations to have significant effects on the dynamics of transient platelet aggregation, i.e., the efficiency of platelet aggregation and characteristics of bond failure, in ways that typify diseased conditions. The GPIb α-vWF-A1 bond formation rate is predicted to have piecewise linear dependence on the prevailing fluid shear rate, with a sharp transition in fluid shear dependency at 7200 s −1. Interplatelet bond force-loading is found to be complex and highly nonlinear. These results demonstrate PAD as a powerful predictive modeling tool for elucidating platelet adhesive phenomena under flow.