Elongational Flow Induces the Unfolding of von Willebrand Factor at Physiological Flow Rates

The unfolding of von Willebrand Factor (vWF), one of the largest multimeric proteins in our body, has been shown to be a crucial step in the process of blood clotting. Here we show that elongational flows, which appear during vasoconstriction or stenosis, are the primary activation mechanisms of vWF, and unfold the multimeric protein at flow rates that are two orders-of-magnitude below those corresponding to pure shear. The findings presented here complement the current understanding of blood clotting from the molecular to the physiological level, and provide new physical insights into the connection between clotting anomalies, such as Heyde's syndrome and stenosis. These findings also represent a new paradigm in the function and activation of vWF.