A Biophysics-Based Mathematical Model of Shear-Induced Platelet Activation and Receptor Shedding: Re-Examining Previous Experimental Data.

Abstract

The power-law model, originally developed for shear-induced hemolysis, has been used to predict shear-induced platelet activation and receptor shedding. However, its empirical nature lacks mechanistic explanations and violates physical reality by not imposing an upper limit, often leading to inaccuracies. Recent studies suggest that the mechanical pulling of platelet GPIb-IX complex triggers the unfolding of its mechanosensitive domain, a crucial process to platelet activation, which can be explained by Bell's model of bond unbinding under force. Motivated by these findings, we propose a novel mathematical model for shear-induced platelet activation (P-selectin) and shear-induced platelet receptor (glycoprotein Ibα [GPIbα], GPVI, and GPIIb/IIIa) shedding based on the principle of bond unbinding. The model was examined using experimental data from previous studies in which blood samples were exposed to different combinations of constant shear stress and exposure time. The new model demonstrated an excellent fit with experimental data with an overall coefficient of determination R2 >0.8, mapping the trends in platelet activation and receptor shedding (except for GPIIb/IIIa) across a range of shear conditions. This new model not only addresses the intrinsic upper bound error in the power-law model but also provides a theoretical foundation into blood damage under shear stress.