title: Mechanical stretch induces clustering of beta1-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 beta1-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 beta1-integrins in this process. This was confirmed using a functional blocking antibody directed against beta1-integrins which reversed the stretch-induced adhesion. Furthermore, mechanical stretch gives rise to a rapid redistribution of beta1-integrins in clusters on the basal cell membrane, without changing the overall amount of this particular integrin subset. Concomitantly, the EGFR co-localizes with beta1-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 beta1-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 beta1-integrins and EGFR in the adhesion complex supporting the transmission of stretch-induced signals.
authors.affiliation: Department of Dermatology and Venerology, University Hospital, Johann Wolfgang Goethe-University, Frankfurt/Main, Germany.
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Knies
authors.forename: August
authors.initials: A
authors.lastname: Bernd
authors.forename: Roland
authors.initials: R
authors.lastname: Kaufmann
authors.forename: Jürgen
authors.initials: J
authors.lastname: Bereiter-Hahn
authors.forename: Stefan
authors.initials: S
authors.lastname: Kippenberger
mesh_terms: D002448:Cell Adhesion; D002460:Cell Line; D066246:ErbB Receptors / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D019012:Integrin beta1 / Q000378:metabolism*; D015603:Keratinocytes / Q000378:metabolism / Q000502:physiology*; D018613:Microscopy, Confocal; D013314:Stress, Mechanical
chemical_list: D019012:Integrin beta1; D066246:ErbB Receptors; D048049:Extracellular Signal-Regulated MAP Kinases