Platelets drive fibronectin fibrillogenesis using integrin αIIbβ3.pdf (2.21 MB)
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Platelets drive fibronectin fibrillogenesis using integrin αIIbβ3

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journal contribution
posted on 08.06.2022, 15:52 by Sebastian Lickert, Martin KennyMartin Kenny, Kateryna Selcuk, Johanna L Mehl, Markus Bender, Susanna M Früh, Melanie A Burkhardt, Jan-Dirk Studt, Bernhard Nieswandt, Ingmar SchoenIngmar Schoen, Viola Vogel
Platelets interact with multiple adhesion proteins during thrombogenesis, yet little is known about their ability to assemble fibronectin matrix. In vitro three-dimensional superresolution microscopy complemented by biophysical and biochemical methods revealed fundamental insights into how platelet contractility drives fibronectin fibrillogenesis. Platelets adhering to thrombus proteins (fibronectin and fibrin) versus basement membrane components (laminin and collagen IV) pull fibronectin fibrils along their apical membrane versus underneath their basal membrane, respectively. In contrast to other cell types, platelets assemble fibronectin nanofibrils using αIIbβ3 rather than α5β1 integrins. Apical fibrillogenesis correlated with a stronger activation of integrin-linked kinase, higher platelet traction forces, and a larger tension in fibrillar-like adhesions compared to basal fibrillogenesis. Our findings have potential implications for how mechanical thrombus integrity might be maintained during remodeling and vascular repair.

Funding

ETH Zurich, Swiss TransMed “Life Matrix” 33/2013

Wyss Zurich

Velux Stiftung

TR240 grant with project number 374031971 of the Deutsche Forschungsgemeinschaft (DFG; German Research Foundation)

Science Foundation Ireland under grant number 19/FFP/6708

Royal College of Surgeons in Ireland

European Union’s Horizon 2020 research and innovation programme under grant agreement no. 747586

History

Comments

The original article is available at https://www.science.org/

Published Citation

Lickert S. et al. Platelets drive fibronectin fibrillogenesis using integrin αIIbβ3. Sci Adv. 2022;8(10):eabj8331

Publication Date

11 Mar 2022

PubMed ID

35275711

Department/Unit

  • Irish Centre for Vascular Biology
  • School of Pharmacy and Biomolecular Sciences

Research Area

  • Vascular Biology
  • Biomaterials and Regenerative Medicine

Publisher

American Association for the Advancement of Science (AAAS)

Version

  • Published Version (Version of Record)