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

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.