Mesoscopic modeling of VWF collapsible dynamics under shear incorporating solvation effect*

VWF is a collapsible polymer in blood that controls primary hemostasis. The activation of VWF is through a mechanosensitive process triggered by viscous shear that can unfold VWF and exposes its binding sites. While it is known in polymer physics that solvent quality affects the polymer collapsible dynamics, existing biophysical models of VWF largely neglect the solvation effect. Since solvent quality of blood can change in experimental and biological settings (such as those in diabetes), current biophysical models of VWF can fail to predict the mechano-activation of VWF in blood. To address this limitation, we have developed a mesoscopic model of VWF to incorporate many-body hydrodynamic effect as well as the molecular solvation effect. Without including explicitly the solvent-particle intermolecular interactions, we show that our model can capture the competition between the viscous effect and the solvent-induced molecular effects while changing the solvent quality (from good to poor). We further demonstrate that the improved VWF model can be applied to model VWF-glucose interactions in hyperglycemic blood, providing new insights that can be applied to address existing controversies regarding VWF shear-induced activation.