Abstract
Shear-induced conformational changes of von Willebrand factor (VWF) play an important role in platelet activation. A novel approach describing VWF unfolding on the platelet surface under dynamic shear stress is proposed. Cumulative effect of dynamic shear on platelet activation via conformational changes of VWF is analysed. The critical condition of shear-induced platelet activation is formulated. The explicit expression for the threshold value of cumulative shear stress as a function of VWF multimer size is derived. The results open novel prospects for pharmacological regulation of shear-induced platelet activation through control of VWF multimers size distribution.
Highlights
It is known that high shear stresses induce platelet activation and subsequent aggregation [1,2,3,4]
We investigate the conditions of von Willebrand factor (VWF) molecule total unfolding under the dynamic action of unsteady shear stress
The central question is as follows: what are the conditions for irreversible conformational unfolding of VWF? Looking for the answer to this question, it seems appropriate to build phase portraits of the considered system in accordance with standard methods of analytical mechanics [38]
Summary
It is known that high shear stresses induce platelet activation and subsequent aggregation [1,2,3,4]. This process is premised on the conformational unfolding of von Willebrand factor (VWF) molecules. VWF multimers unfold, exposing more A1 domains capable of binding platelet receptors GPIb [5,6,7,8,9]. The initial activation of platelet signal cascades is triggered by the simultaneous coating of several GPIb receptors with A1 domains of a VWF molecule [10,11,12]. SIPA has been intensively investigated in vivo and in vitro [17,18,19]
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