EGFR activation attenuates the mechanical threshold for integrin tension and focal adhesion formation

• Type of Material: Article
• Authors: Tejeshwar C Rao, The University of Alabama at Birmingham; Victor PY Ma, Emory University; Aaron Blanchard, Emory University; Tara M Urner, The University of Alabama at Birmingham; Shreya Grandhi, The University of Alabama at Birmingham; Khalid Salaita, Emory University; Alexa L Mattheyses, The University of Alabama at Birmingham
• Language: English
• Date: 2020-07-10
• Publisher: The Company of Biologists.
• Publication Version: Final Published Version
• Copyright Statement: © 2020. Published by The Company of Biologists Ltd
• Final Published Version (URL): http://dx.doi.org/10.1242/jcs.238840
• Title of Journal or Parent Work: Journal of Cell Science
• Volume: 133
• Issue: 13
• Grant/Funding Information: This work was supported by funding to A.L.M. from the National Science Foundation (NSF) CAREER (1832100) and to A.L.M. and K.S. from the National Institutes of Health (NIH) (R01GM131099). Deposited in PMC for release after 12 months.
• Keywords: Mechanotransduction; Force probes; Focal Adhesions; Cell Adhesion; Integrin; ErbB Receptors; Integrins; Signal Transduction
• Research Categories: Chemistry, General; Biology, Cell; Engineering, Biomedical

Abstract

Mechanical forces, growth factors and the extracellular matrix all play crucial roles in cell adhesion. To understand how epidermal growth factor receptor (EGFR) impacts the mechanics of adhesion, we employed tension gauge tether (TGT) probes displaying the integrin ligand cRGDfK and quantified integrin tension. EGF exposure significantly increased spread area, cell circularity, integrated integrin tension, mechanical rupture density, radial organization and size of focal adhesions in Cos-7 cells on TGT surfaces. These findings suggest that EGFR regulates integrin tension and the spatial organization of focal adhesions. Additionally, we found that the mechanical tension threshold for outside-in integrin activation is tunable by EGFR. Parallel genetic and pharmacologic strategies demonstrated that these phenotypes are driven by ligand-dependent EGFR signaling. Our results establish a novel mechanism whereby EGFR regulates integrin activation and cell adhesion, providing control over cellular responses to the environment.