Behavior of Von Willebrand Factor (VWF) and platelet interaction under shear flow

Von Willebrand Factor (VWF) captures platelets under high shear by unfolding to elongated form under hydrodynamic stress exposing binding sites. Recent studies (Fu et al, Nature Comm. 2017) show that subsequent to elongation of VWF, there is a second step local-tension-dependent transition to a high affinity state with GPIbα. High-affinity sites develop only in regions of VWF where local tension exceeds ~21 pN. Thus, local tension within VWF monomers should also be considered in platelet binding. Our model captures the dynamics of entangled multi-VWF chains, but also reformulates binding kinetics based on local tension in the VWF strand matching the critical shear rates for extension at 6500/s for soluble VWF (sVWF), <1000/s for individual immobilized VWF (iVWF), and 3500-9000/s for bundled iVWF. We show that at 6500/s, while iVWF (5 A1/µm²) form elongated entangled bundles, the iVWF bundles alone are unable to capture fast-flowing platelets since more than 60% of the dimers have local tension <5 pN. Only dimers near the anchored position experience tension >20 pN, which is thought to induce high affinity bonds to GPIbα. However, with sVWF at plasma concentration (1.0E13/mL), we show that rapid platelet immobilization/capture requires formation of network of iVWF-sVWF bundles.