Single-molecule force measurements of the polymerizing dimeric subunit of von Willebrand factor

Sithara S. Wijeratne, Jingqiang Li, Hui-Chun Yeh, Leticia Nolasco, Zhou Zhou, Angela Bergeron, Eric W. Frey, Joel L. Moake, Jing-fei Dong, and Ching-Hwa Kiang
Phys. Rev. E 93, 012410 – Published 21 January 2016

Abstract

Von Willebrand factor (VWF) multimers are large adhesive proteins that are essential to the initiation of hemostatic plugs at sites of vascular injury. The binding of VWF multimers to platelets, as well as VWF proteolysis, is regulated by shear stresses that alter VWF multimeric conformation. We used single molecule manipulation with atomic force microscopy (AFM) to investigate the effect of high fluid shear stress on soluble dimeric and multimeric forms of VWF. VWF dimers are the smallest unit that polymerizes to construct large VWF multimers. The resistance to mechanical unfolding with or without exposure to shear stress was used to evaluate VWF conformational forms. Our data indicate that, unlike recombinant VWF multimers (RVWF), recombinant dimeric VWF (RDVWF) unfolding force is not altered by high shear stress (100dynes/cm2 for 3 min at 37C). We conclude that under the shear conditions used (100dynes/cm2 for 3 min at 37C), VWF dimers do not self-associate into a conformation analogous to that attained by sheared large VWF multimers.

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  • Received 27 May 2015
  • Revised 3 December 2015

DOI:https://doi.org/10.1103/PhysRevE.93.012410

©2016 American Physical Society

Physics Subject Headings (PhySH)

Physics of Living Systems

Authors & Affiliations

Sithara S. Wijeratne1, Jingqiang Li1, Hui-Chun Yeh2, Leticia Nolasco3, Zhou Zhou4, Angela Bergeron2, Eric W. Frey1, Joel L. Moake3, Jing-fei Dong4, and Ching-Hwa Kiang1,3,*

  • 1Department of Physics and Astronomy, Rice University, Houston, Texas 77005, USA
  • 2Thrombosis Division, Section of Cardiovascular Sciences, Department of Medicine, Baylor College of Medicine, Houston, Texas 77005, USA
  • 3Department of Bioengineering, Rice University, Houston, Texas 77005, USA
  • 4Puget Sound Blood Center and Division of Hematology, Department of Medicine, University of Washington, Seattle, Washington 98104, USA

  • *chkiang@rice.edu

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Vol. 93, Iss. 1 — January 2016

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