Mechanical stretch induces clustering of β1‐integrins and facilitates adhesion

Abstract: Human epithelial cells are permanently stimulated by external mechanical forces. The present in vitro study suggests that keratinocytes respond to mechanical strain by a coordinated spatial and functional utilization of β1‐integrins and the epidermal growth factor receptor (EGFR) with impact to the adhesion properties. It was found that a single mechanical stretch applied to HaCaT keratinocytes elevates the substrate adhesion, in particular to fibronectin and collagen type IV but not to laminin indicating the relevance of β1‐integrins in this process. This was confirmed using a functional blocking antibody directed against β1‐integrins which reversed the stretch‐induced adhesion. Furthermore, mechanical stretch gives rise to a rapid redistribution of β1‐integrins in clusters on the basal cell membrane, without changing the overall amount of this particular integrin subset. Concomitantly, the EGFR co‐localizes with β1‐integrin suggesting a functional cooperation of both membrane proteins in mechano‐signaling. This is corroborated by data showing that stretch‐induced activation of the EGFR and the downstream element extracellular regulated kinase 1/2 (ERK1/2) is reversed by preincubation with β1‐integrin antibodies. Vice versa, blocking the EGFR using a specific inhibitor abrogates stretch‐induced ERK1/2 activation. In summary, these results show a functional cooperation of β1‐integrins and EGFR in the adhesion complex supporting the transmission of stretch‐induced signals.