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Mechanical activation of a multimeric adhesive protein through domain conformational change

Authors :
Eric W. Frey
Nancy A. Turner
Ching-Hwa Kiang
Joel L. Moake
Sithara S. Wijeratne
Hui Chun Yeh
Jing-fei Dong
Eric Botello
Leticia Nolasco
Angela L. Bergeron
Zhou Zhou
Jay M. Patel
Source :
Physical review letters. 110(10)
Publication Year :
2012

Abstract

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 multimeric VWF. We found that shear-activated pVWF multimers (spVWF) are more resistant to mechanical unfolding than non-sheared pVWF multimers, as indicated in the higher peak unfolding force. These results provide insight into the mechanism of shear-induced activation of pVWF multimers.

Details

ISSN :
10797114
Volume :
110
Issue :
10
Database :
OpenAIRE
Journal :
Physical review letters
Accession number :
edsair.doi.dedup.....95452a4afafa69716e600a462fe1c681