Initiation of fibronectin fibrillogenesis is an enzyme-dependent process

Shay Melamed, Shelly Zaffryar-Eilot, Elisabeth Nadjar-Boger, Rohtem Aviram, Huaning Zhao, Wesal Yaseen-Badarne, Rotem Kalev-Altman, Dalit Sela-Donenfeld, Oded Lewinson, Sophie Astrof, Peleg Hasson*, Haguy Wolfenson*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Fibronectin fibrillogenesis and mechanosensing both depend on integrin-mediated force transmission to the extracellular matrix. However, force transmission is in itself dependent on fibrillogenesis, and fibronectin fibrils are found in soft embryos where high forces cannot be applied, suggesting that force cannot be the sole initiator of fibrillogenesis. Here, we identify a nucleation step prior to force transmission, driven by fibronectin oxidation mediated by lysyl oxidase enzyme family members. This oxidation induces fibronectin clustering, which promotes early adhesion, alters cellular response to soft matrices, and enhances force transmission to the matrix. In contrast, absence of fibronectin oxidation abrogates fibrillogenesis, perturbs cell-matrix adhesion, and compromises mechanosensation. Moreover, fibronectin oxidation promotes cancer cell colony formation in soft agar as well as collective and single-cell migration. These results reveal a force-independent enzyme-dependent mechanism that initiates fibronectin fibrillogenesis, establishing a critical step in cell adhesion and mechanosensing.

Original languageAmerican English
Article number112473
JournalCell Reports
Volume42
Issue number5
DOIs
StatePublished - 30 May 2023

Bibliographical note

Publisher Copyright:
© 2023

Keywords

  • CP: Cell biology
  • cell adhesion
  • fibronectin fibrillogenesis
  • lysyl oxidaze family
  • mechanosensing

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