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

Abstract

Mechanical forces, growth factors, and the extracellular matrix all play critical 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 during cell adhesion. EGF exposure increased spread area, cell circularity, integrated integrin tension, mechanical rupture density, radial organization and size of focal adhesions (FAs) significantly in Cos-7 cells on TGT surfaces. These findings suggest EGFR regulates integrin tension and FA spatial organization. Additionally we found 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 signalling. Our results establish a novel mechanism where EGFR regulates integrin activation and cell adhesion, providing control over cellular responses to the environment.