Shear-Dependent Interactions of von Willebrand Factor with Factor VIII and Protease ADAMTS 13 Demonstrated at a Single Molecule Level by Atomic Force Microscopy

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• 作者：Klaus Bonazza ; Hanspeter Rottensteiner ; Gerald Schrenk ; Johannes Frank ; G眉nter Allmaier ; Peter L. Turecek ; Friedrich Scheiflinger ; Gernot Friedbacher
• 刊名：Analytical Chemistry
• 出版年：2015
• 出版时间：October 20, 2015
• 年：2015
• 卷：87
• 期：20
• 页码：10299-10305
• 全文大小：412K
• ISSN：1520-6882

文摘

Vital functions of mammals are only possible due to the behavior of blood to coagulate most efficiently in vessels with particularly high wall shear rates. This is caused by the functional changes of the von Willebrand Factor (VWF), which mediates coagulation of blood platelets (primary hemostasis) especially when it is stretched under shear stress. Our data show that shear stretching also affects other functions of VWF: Using a customized device to simulate shear conditions and to conserve the VWF molecules in their unstable, elongated conformation, we visualize at single molecule level by AFM that VWF is preferentially cleaved by the protease ADAMTS13 at higher shear rates. In contrast to this high shear-rate-selective behavior, VWF binds FVIII more effectively only below a critical shear rate of 鈭?0.000 s^鈥?, indicating that under harsh shear conditions FVIII is released from its carrier protein. This may be required to facilitate delivery of FVIII locally to promote secondary hemostasis.