ArticleProceedings of the National Academy of Sciences of the United States of America2016
Force sensing by the vascular protein von Willebrand factor is tuned by a strong intermonomer interaction.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 61 citations in OpenAlex.
- Functional Characterization of the VWF p.Cys2163Tyr Variant Reveals Impaired Secretion and Intracellular Processing.Biomolecules · 2026Article
- Effect of Pulse Frequency on Shear-Induced Extension of Von Willebrand Factor in Continuous-Flow Ventricular Assist Device (CF-VAD).ASAIO journal (American Society for Artificial Internal Organs : 1992) · 2026Article
- Identification of missense variants in the C-domains of von Willebrand factor that cause gain-of-function-like activity.Blood advances · 2026Article
- Protein force spectroscopy using magnetic tweezers: Slow and steady wins the race?Biophysical journal · 2026Review
- FRET Visualization of High Mechanosensation of von Willebrand Factor to Hydrodynamic Force.Biosensors · 2025Article
- Article
- Von Willebrand factor and hematogenous cancer metastasis under flow.Frontiers in cell and developmental biology · 2024Review
- Investigation of metal ion binding biomolecules one molecule at a time.Frontiers in chemistry · 2024Review
- The interplay between adsorption and aggregation of von Willebrand factor chains in shear flows.Biophysical journal · 2023Article
- Biomechanical activation of blood platelets via adhesion to von Willebrand factor studied with mesoscopic simulations.Biomechanics and modeling in mechanobiology · 2023Article
- Cadmium, von Willebrand factor and vascular aging.npj aging · 2023Review
- Structural hierarchy of mechanical extensibility in human von Willebrand factor multimers.Protein science : a publication of the Protein Society · 2023Article
- A conformational transition of the D'D3 domain primes von Willebrand factor for multimerization.Blood advances · 2022Article
- The N-terminal autoinhibitory module of the A1 domain in von Willebrand factor stabilizes the mechanosensor catch bond.RSC chemical biology · 2022Article
- Engineered Molecular Therapeutics Targeting Fibrin and the Coagulation System: a Biophysical Perspective.Biophysical reviews · 2022Review
- SARS-CoV-2 infection and oxidative stress: Pathophysiological insight into thrombosis and therapeutic opportunities.Cytokine & growth factor reviews · 2022Review
- Gain-of-Function Variant p.Pro2555Arg of von Willebrand Factor Increases Aggregate Size through Altering Stem Dynamics.Thrombosis and haemostasis · 2022Article
- Exposure of Von Willebrand Factor Cleavage Site in A1A2A3-Fragment under Extreme Hydrodynamic Shear.Polymers · 2021Article
- Activation of von Willebrand factor via mechanical unfolding of its discontinuous autoinhibitory module.Nature communications · 2021Article
- Review
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The large plasma glycoprotein von Willebrand factor (VWF) senses hydrodynamic forces in the bloodstream and responds to elevated forces with abrupt elongation, thereby increasing its adhesiveness to platelets and collagen. Remarkably, forces on VWF are elevated at sites of vascular injury, where VWF's hemostatic potential is important to mediate platelet aggregation and to recruit platelets to the subendothelial layer. Adversely, elevated forces in stenosed vessels lead to an increased risk of VWF-mediated thrombosis. To dissect the remarkable force-sensing ability of VWF, we have performed atomic force microscopy (AFM)-based single-molecule force measurements on dimers, the smallest repeating subunits of VWF multimers. We have identified a strong intermonomer interaction that involves the D4 domain and critically depends on the presence of divalent ions, consistent with results from small-angle X-ray scattering (SAXS). Dissociation of this strong interaction occurred at forces above [Formula: see text]50 pN and provided [Formula: see text]80 nm of additional length to the elongation of dimers. Corroborated by the static conformation of VWF, visualized by AFM imaging, we estimate that in VWF multimers approximately one-half of the constituent dimers are firmly closed via the strong intermonomer interaction. As firmly closed dimers markedly shorten VWF's effective length contributing to force sensing, they can be expected to tune VWF's sensitivity to hydrodynamic flow in the blood and to thereby significantly affect VWF's function in hemostasis and thrombosis.
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