The N-terminal autoinhibitory module of the A1 domain in von Willebrand factor stabilizes the mechanosensor catch bond

Zhao, Yunduo Charles; Wang, Haoqing; Wang, Yao; Lou, Jizhong; Ju, Lining Arnold

doi:10.1039/d2cb00010e

Cited by 15 publications

(16 citation statements)

References 74 publications

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“…( 2008 ); Zhao et al. ( 2022 )) and its effect on long-term ( s) dynamics of adherent platelets in shear remain out of the scope of the present study and should be addressed in future. Finally, in present work we use a parallel-plane geometry of the system, similar to a typical microfluidic flow chambers or lab-on-a-chip devices for laboratory studies of platelet hemostasis (Six et al.…”

Section: Discussionmentioning

confidence: 94%

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Biomechanical activation of blood platelets via adhesion to von Willebrand factor studied with mesoscopic simulations

Belyaev

Kushchenko

2023

Biomech Model Mechanobiol

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Platelet adhesion and activation are essential initial processes of arterial and microvascular hemostasis, where high hydrodynamic forces from the bloodflow impede coagulation. The process relies on von Willebrand factor (VWF)—a linear multimeric protein of blood plasma plays a pivotal role in mechanochemical regulation of shear-induced platelet aggregation (SIPA). Adhesive interactions between VWF and glycoprotein receptors GPIb are crucial for platelet recruitment under high shear stress in fluid. Recent advances in experimental studies revealed that mechanical tension on the extracellular part of GPIb may trigger a cascade of biochemical reactions in platelets leading to activation of integrins (also known as GPIIb/IIIa) and strengthening of the adhesion. The present paper is aimed at investigation of this process by three-dimensional computer simulations of platelet adhesion to surface-grafted VWF multimers in pressure-driven flow of platelet-rich plasma. The simulations demonstrate that GPIb-mediated mechanotransduction is a feasible way of platelet activation and stabilization of platelet aggregates under high shear stress. Quantitative understanding of mechanochemical processes involved in SIPA would potentially promote the discovery of new anti-platelet medication and the development of multiscale numerical models of platelet thrombosis and hemostasis. Supplementary Information The online version contains supplementary material available at 10.1007/s10237-022-01681-3.

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Section: Discussionmentioning

confidence: 94%

“…( 2021 ); Zhao et al. ( 2022 )). The typical tension force required for activation of VWF monomers was estimated as 20–35 pN by Fu et al.…”

Section: Introductionmentioning

confidence: 99%

Biomechanical activation of blood platelets via adhesion to von Willebrand factor studied with mesoscopic simulations

Belyaev

Kushchenko

2023

Biomech Model Mechanobiol

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“…Aside from the conventional BFP, advancements in the setup have led to the development of both a dual BFP and fluorescent BFP setup. The BFP-DFS applications include but are not limited to ligand binding kinetics [14][15][16][17][18][19] , cytoskeleton mediated receptor activation [20][21][22][23][24] , 2D receptor conformational changes 25,26 and dual receptor crosstalk 27,28 . More broadly, the elucidation of these mechanisms has contributed significantly to research in the fields of cancer biology, thrombosis, and inflammation.…”

Section: Introductionmentioning

confidence: 99%

Biomembrane Force Probe (BFP): Designs, advancements and recent applications to live-cell mechanobiology

Moldovan

Song

Chen

et al. 2023

Preprint

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Mechanical forces play a crucial role in biological processes at the molecular and cellular levels. Recent advancements in dynamic force spectroscopies (DFS) have enabled the application and measurement of forces and displacements with high resolutions, providing insights into the mechanical pathways involved in various diseases, including cancer, cardiovascular disease, and COVID-19. Among the various DFS techniques, biomembrane force probe (BFP) advancements have improved our ability to measure bond kinetics and cellular mechanosensing with pico-newton and nano-meter resolutions. In this review, we provide a comprehensive overview of the classical BFP-DFS setup and highlight key advancements, including the development of dual biomembrane force probe (dBFP) and fluorescence biomembrane force probe (fBFP). BFP-DFS not only enables the investigation of dynamic bond behaviors on living cells, but also contributed significantly to our understanding of the specific ligand–receptor axes mediated cell mechanosensing. Besides, we explore the contribution of discoveries made possible by BFP-DFS in cancer biology, thrombosis, and inflammation, as well as predict future BFP upgrades to improve output and feasibility. Although BFP-DFS is still a niche research modality, its contribution to the growing field of cell mechanobiology is unparalleled, and its potential to elucidate novel therapeutic discoveries is significant.

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“…Understanding the structural insights underlying A1-GPIba interaction dynamics is significant towards developing novel anti-thrombotic therapeutics. 10,46,47 Nevertheless, how N-AIM or Lp interacts with A1-GPIba in trans and affects catch bond behaviors remains elusive. To this end, the present study aims to employ a series of computational biology platforms to predict soluble Lp conformation and to define its role in regulating A1-GPIba catch bond.…”

Section: Introductionmentioning

confidence: 99%

“…By combining the biomembrane force probe (BFP), MD simulation and microfluidic perfusion assays, our recent study demonstrated that N-AIM stabilizes A1 catch bond behavior and serves as a mechano-regulator of VWF activity in cis . 46 10 Clinically, the FDA has recently approved Anti-VWF Caplacizumab (ALX-0081) to treat thrombotic thrombocytopenic purpura (TTP) with less bleeding side effects. 26 Its epitope has subsequently mapped to the N-AIM sequence of VWF A1 domain.…”

Section: Introductionmentioning

confidence: 99%

The soluble N-terminal autoinhibitory module of the A1 domain in von Willebrand factor partially suppresses its catch bond with glycoprotein Ibα in a sandwich complex

Zhao

2022

Phys. Chem. Chem. Phys.

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The N-terminal autoinhibitory module of the A1 domain in von Willebrand factor stabilizes the mechanosensor catch bond

Abstract: The N-AIM of VWF-A1 forms a Rotini-like structure, therefore partially autoinhibit VWF-A1–GPIbα interaction. The N-AIM acts as a defending sword to protect and stabilize the VWF-A1 structure under harsh environments.

Cited by 15 publications

References 74 publications

Biomechanical activation of blood platelets via adhesion to von Willebrand factor studied with mesoscopic simulations

Biomechanical activation of blood platelets via adhesion to von Willebrand factor studied with mesoscopic simulations

Biomembrane Force Probe (BFP): Designs, advancements and recent applications to live-cell mechanobiology

The soluble N-terminal autoinhibitory module of the A1 domain in von Willebrand factor partially suppresses its catch bond with glycoprotein Ibα in a sandwich complex

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