Fibroblasts Close a Void in Free Space by a Purse-String Mechanism

Abstract

The mechanism by which stromal cells fill voids in injured tissue remains a fundamental question in regenerative medicine. While it is well-established that fibroblasts fill voids by depositing extracellular matrix (ECM) proteins as they migrate toward the wound site, little is known about their ability to adopt an epithelial-like purse-string behavior. To investigate fibroblast behavior during gap closure, we created an artificial wound with a large void space. We discovered that fibroblasts could form a freestanding bridge over deep microvoids, closing the void via purse string contraction, a mechanism previously thought to be unique to epithelial wound closure. The findings also revealed that myosin II mediated contractility and intercellular adherent junctions were required for the closure of the fibroblast gap in our fabricated threedimensional artificial wound. To fulfill their repair function under the specific microenvironmental conditions of wounds, fibroblasts appeared to acquire the structural features of epithelial cells, namely, contractile actin bundles that span over multiple cells along the boundary. These findings shed light on a novel mechanism by which stromal cells bridge the 3D gap during physiological processes such as morphogenesis and wound healing.