Coarse-Grain Modeling of Shear-Induced Binding between von Willebrand Factor and Collagen.

Von Willebrand factor (VWF) is a large multimeric protein that aids in blood clotting. Near injury sites, hydrodynamic force from increased blood flow elongates VWF, exposing binding sites for platelets and collagen. To investigate VWF binding to collagen that is exposed on injured arterial surfaces, Brownian dynamics simulations are performed with a coarse-grain molecular model. Accounting for hydrodynamic interactions in the presence of a stationary surface, shear flow conditions are modeled. Binding between beads in coarse-grain VWF and collagen sites on the surface is described via reversible ligand-receptor-type bond formation, which is governed via Bell model kinetics. For conditions in which binding is energetically favored, the model predicts a high probability for binding at low shear conditions; this is counter to experimental observations but in agreement with what prior modeling studies have revealed. To address this discrepancy, an additional binding criterion that depends on the conformation of a submonomer feature in the model local to a given VWF binding site is implemented. The modified model predicts shear-induced binding, in very good agreement with experimental observations; this is true even for conditions in which binding is significantly favored energetically. Biological implications of the model modification are discussed in terms of mechanisms of VWF activity.