Effects of hydrophobicity, tethering and size on flow-induced activation of von Willebrand factor multimers

Von Willebrand factor (VWF) is a multimeric protein of blood plasma that mediates platelet adhesion to injury under strong hemodynamic flows in arterias and microvasvulature. We present a 3D coarse-grained computer model of VWF multimers in flowing viscous fluid that explicitely grasps the dynamics, the conformational changes and the hydrodynamics-induced activation of adhesivity of these protein concatamers to GPIb receptor of blood platelets. The model is based on the fluctuating Lattice Boltzmann method for modelling the hydrodynamics in the simulation box and the Lagrangian particle dynamics coupled to the fluid by a viscous drag force. The model has been validated by the comparison with the experimental data found in literature. We studied the effect of hydrophobic interactions on the conformational dynamics of VWF multimers. The simulations suggest that the contour length is an important parameter that controls the functionality of VWF multimers in blood. We also demonstrate that tethering to the surface of a vessel wall promoted the flow-induced activation of VWF, while those multimers that remain untethered and move freely in the blood plasma require a stronger shearing to get activated. © 2019