2020.04.20.050708.full.pdf (2.95 MB)

Platelets exploit fibrillar adhesions to assemble fibronectin matrix revealing new force-regulated thrombus remodeling mechanisms

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journal contribution
posted on 02.07.2021, 16:23 by Sebastian Lickert, Kateryna Selcuk, Martin Kenny, Johanna L Mehl, Susanna M Früh, Melanie A Burkhardt, Jan-Dirk Studt, Ingmar Schoen, Viola Vogel
Upon vascular injury, platelets are crucial for thrombus formation and contraction, but do they directly initiate early tissue repair processes? Using 3D super-resolution microscopy, micropost traction force microscopy, and specific integrin or myosin IIa inhibitors, we discovered here that platelets form fibrillar adhesions. They assemble fibronectin nanofibrils using αIIbβ3 (CD41/CD61, GPIIb-IIIa) rather than α5β1 integrins, in contrast to fibroblasts. Highly contractile platelets in contact with thrombus proteins (fibronectin, fibrin) pull fibronectin fibrils along their apical membrane, whereas platelets on basement membrane proteins (collagen IV, laminin) are less contractile generating less stretched planar meshworks beneath themselves. As probed by vinculin-decorated talin unfolding, platelets on fibronectin generate similar traction forces in apical fibrillar adhesions as fibroblasts do. These are novel mechanobiology mechanisms by which platelets spearhead the fibrillogenesis of the first de novo ECM, including its 2D versus 3D network architectures depending on their ECM environment, and thereby pave the way for cell infiltration.

Funding

European Union’s Horizon 2020 research and innovation programme under grant agreement No 747586 (I.S.)

ETH Zurich

Swiss TransMed "Life Matrix" 33/2013

Wyss Zurich

Velux Stiftung

RCSI

History

Comments

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

Published Citation

Lickert S, et al. Platelets exploit fibrillar adhesions to assemble fibronectin matrix revealing new force-regulated thrombus remodeling mechanisms. bioRxiv 2020.04.20.050708

Publication Date

20 April 2020

Department/Unit

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

Research Area

  • Biomaterials and Regenerative Medicine
  • Vascular Biology

Publisher

Cold Spring Harbor Laboratory

Version

  • Submitted Version (Preprint)