The diffusion of normal skin wound myofibroblast-derived microvesicles differs according to matrix composition

Abstract

Microvesicles (MVs) are a subtype of extracellular vesicles that can transfer biological information over long distances, affecting normal and pathological processes including skin wound healing. However, the diffusion of MVs into tissues can be impeded by the extracellular matrix (ECM). We investigated the diffusion of dermal wound myofibroblast-derived MVs into the ECM by using hydrogels composed of different ECM molecules such as fibrin, type III collagen and type I collagen that are present during the healing process. Fluorescent MVs mixed with hydrogels were employed to detect MV diffusion using fluorometric methods. Our results showed that MVs specifically bound type I collagen and diffused freely out of fibrin and type III collagen. Further analysis using flow cytometry and specific inhibitors revealed that MVs bind to type I collagen via the α2β1 integrin. These data demonstrate that MV transport depends on the composition of the wound environment.