Mg²⁺ and Ca²⁺ differentially regulate β₁ integrin-mediated adhesion of dermal fibroblasts and keratinocytes to various extracellular matrix proteins

The specific requirements for divalent cations in the integrin-dependent adhesion and deadhesion of human dermal fibroblasts and human epidermal keratinocytes to various extracellular matrix proteins have been studied in vitro. The adhesion of both cell types to collagen type I and to laminin was enhanced by Mg²⁺ in a concentration-dependent manner, while Ca²⁺ dose-dependently antagonized this effect, thus promoting deadhesion. The cation-dependent conversion between adhesion and deadhesion occurred already at 2 to 10 min after addition of the alternate cation and was almost completed at 20 min. Interestingly, Ca²⁺ could not reverse the Mg²⁺-enhaneed adhesion of both cell types to fibronectin. Inhibition studies with function-blocking antibodies directed against distinct β₁ integrins showed that the Mg²⁺-enhanced fibroblast adhesion to collagen type I was mediated by the α₁β₁ and the α₂β₁ integrins, whereas keratinocyte adhesion to collagen type I was mediated by the α₂β₁ integrin. Both cell types utilized the α₂β₁ and the α₆β₁ integrins for Mg²⁺-dependent adhesion to laminin and the α₅β₁ integrin for the adhesion to fibronectin. Integrin expression at the cell surface was not altered, indicating that divalent cation-dependent conformational changes of β₁ integrins most likely regulate their functional activity.