Platelet activation via dynamic conformational changes of von Willebrand factor under shear

Denis M Pushin; Tatiana Y Salikhova; Ksenia E Zlobina; Georgy Th Guria

doi:10.1371/journal.pone.0234501

Platelet activation via dynamic conformational changes of von Willebrand factor under shear

PLoS One. 2020 Jun 11;15(6):e0234501. doi: 10.1371/journal.pone.0234501. eCollection 2020.

Authors

Denis M Pushin^{1

2}, Tatiana Y Salikhova², Ksenia E Zlobina¹, Georgy Th Guria^{1

2}

Affiliations

¹ National Research Center for Hematology, Moscow, Russia.
² Moscow Institute of Physics and Technology, Dolgoprudny, Russia.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Blood Platelets / physiology*
Humans
Models, Biological*
Molecular Dynamics Simulation
Platelet Activation / physiology*
Platelet Glycoprotein GPIb-IX Complex / metabolism
Protein Multimerization / physiology
Protein Stability
Protein Structure, Quaternary / physiology*
Stress, Mechanical
Structure-Activity Relationship
von Willebrand Factor / metabolism*

Substances

Platelet Glycoprotein GPIb-IX Complex
adhesion receptor
von Willebrand Factor

Grants and funding

The work was supported by grant No 19-11-00260 of Russian Science Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.