Divalent cations (Mg2+, Ca2+) differentially influence the β1 integrin‐mediated migration of human fibroblasts and keratinocytes to different extracellular matrix proteins

Thilo Sascha Lange, Katja Kirchberg, Anja Katrin Bielinsky, Andreas Leuker, Ilan Bank, Thomas Ruzicka, Karin Scharffetter‐Kochanek

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Abstract Directed migration of keratinocytes and fibroblasts is a fundamental prerequisite in wound healing. Cation‐dependent affinity changes of integrins are responsible for cell adhesion to and deadhesion from extracellular matrix proteins and have been implicated in driving cell migration. The specific requirements for divalent cations in the integrin‐dependent migration of human dermal fibroblasts and human epidermal keratinocytes to various extracellular matrix proteins have been studied in vitro using blindwell Boyden chambers. The migration of the tested cells to collagen type I was mediated by the α2β2 integrins, to fibronectin by the combined action of the α3β2 and the α5β1 integrin, and the migration of fibroblasts to laminin dependent both on the α2β1 and the α6β1 integrins. No migration of keratinocytes to laminin was detected. Mg2+ alone induced cell migration with an optimum at 2 mM for fibroblasts and at 10 mM for keratinocytes. Ca2+ alone at 2 mM only marginally enhanced fibroblast and keratinocyte migration. At higher concentrations Ca2+ suppressed the stimulatory Mg2+ effect. 2 mM Ca2+ combined with 2 mM Mg2+ showed an additive stimulatory effect on the migration of fibroblasts to fibronectin. These data suggest that extracellular divalent cations differentially influence the integrin‐mediated cell migration. A concentration gradient of Mg2+/Ca2+, as reported in tissue injury, thus may play a regulatory role in cell migration required for tissue remodelling.

Original languageEnglish (US)
Pages (from-to)130-137
Number of pages8
JournalExperimental Dermatology
Issue number3
StatePublished - Jun 1995


  • Ca
  • Mg
  • dermal fibroblasts
  • divalent cations
  • extracellular matrix
  • keratinocytes
  • migration
  • β , integrins

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