Journal
JOURNAL OF CELL SCIENCE
Volume 133, Issue 13, Pages -Publisher
COMPANY BIOLOGISTS LTD
DOI: 10.1242/jcs.238840
Keywords
Integrin; Force probes; Mechanotransduction
Categories
Funding
- National Science Foundation (NSF) CAREER [1832100]
- National Institutes of Health (NIH) [R01GM131099]
- Div Of Molecular and Cellular Bioscience
- Direct For Biological Sciences [1832100] Funding Source: National Science Foundation
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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. This article has an associated First Person interview with the first author of the paper.
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