EGFR and HER2 activate rigidity sensing only on rigid matrices

Mayur Saxena, Shuaimin Liu, Bo Yang, Cynthia Hajal, Rishita Changede, Junqiang Hu, Haguy Wolfenson, James Hone, Michael Sheetz

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

Epidermal growth factor receptor (EGFR) interacts with integrins during cell spreading and motility, but little is known about the role of EGFR in these mechanosensing processes. Here we show, using two different cell lines, that in serum- A nd EGF-free conditions, EGFR or HER2 activity increase spreading and rigidity-sensing contractions on rigid, but not soft, substrates. Contractions peak after 15-20 min, but diminish by tenfold after 4 h. Addition of EGF at that point increases spreading and contractions, but this can be blocked by myosin-II inhibition. We further show that EGFR and HER2 are activated through phosphorylation by Src family kinases (SFK). On soft surfaces, neither EGFR inhibition nor EGF stimulation have any effect on cell motility. Thus, EGFR or HER2 can catalyse rigidity sensing after associating with nascent adhesions under rigidity-dependent tension downstream of SFK activity. This has broad implications for the roles of EGFR and HER2 in the absence of EGF both for normal and cancerous growth.

Original languageEnglish (US)
Pages (from-to)775-781
Number of pages7
JournalNature Materials
Volume16
Issue number7
DOIs
StatePublished - Jul 1 2017
Externally publishedYes

ASJC Scopus subject areas

  • Chemistry(all)
  • Materials Science(all)
  • Condensed Matter Physics
  • Mechanics of Materials
  • Mechanical Engineering

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    Saxena, M., Liu, S., Yang, B., Hajal, C., Changede, R., Hu, J., Wolfenson, H., Hone, J., & Sheetz, M. (2017). EGFR and HER2 activate rigidity sensing only on rigid matrices. Nature Materials, 16(7), 775-781. https://doi.org/10.1038/nmat4893