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

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 free-standing 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 three-dimensional 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.