The mechanical force-induced activation of the adhesive protein von Willebrand factor (VWF), which
experiences high hydrodynamic forces, is essential in initiating platelet adhesion. The importance of the
mechanical force-induced functional change is manifested in the multimeric VWF's crucial role in blood
coagulation, when high fluid shear stress activates plasma VWF (PVWF) multimers to bind platelets.
Here, we showed that a pathological level of high shear stress exposure of PVWF multimers results in
domain conformational changes, and the subsequent shifts in the unfolding force allow us to use force as
a marker to track the dynamic states of the multimeric VWF. We found that shear-activated PVWF
multimers are more resistant to mechanical unfolding than nonsheared PVWF multimers, as indicated in
the higher peak unfolding force. These results provide insight into the mechanism of shear-induced
activation of PVWF multimers
