When cells migrate and spread, they mechanically test the rigidity of the extracellular matrix (ECM) by contracting it, and at certain levels of force, cells reinforce integrin-mediated adhesions. Sheetz and colleagues now show that rigidity sensing is dependent on epidermal growth factor receptor (EGFR) activity, specifically on rigid surfaces (Nat. Mater. http://doi.org/b6wz; 2017).

Seeding cells onto micropillars coated with fibronectin confirms the role of local contractile units in contraction testing, and show that contractile unit activity is reduced on stiff compared with soft pillar matrix. EGFR is known to act with integrins in regulating cell–ECM interactions, and the authors find that loss of EGFR, through inhibition or knockdown, decreases spreading and contractility on stiff, but not on soft substrates. Interestingly, in the absence of EGFR, overexpression of the ligand-independent receptor HER2 can rescue rigidity sensing. The authors go on to show that EGFR can be activated in a ligand-independent manner by Src and, using inhibitors and mutants of Src-dependent phosphorylation sites, they find that this is needed for mechanosensing. However, EGF also stimulates local contraction events on rigid surfaces. Finally, they demonstrate that EGF-mediated activation of motility is dependent on myosin contractility and Src kinases.

These data demonstrate a previously unknown role for EGFR in rigidity sensing.