Computational and Experimental Study of the Mechanics of Embryonic Wound Healing

Abstract

The healing of embryonic wounds yields insight into mechanical forces which shape a developing organism. Here we characterize healing of wounds in epithelia of early stage chick embryos, and use a newly developed computational model to investigate underlying cellular-level mechanisms. Early stage chick embryos, consisting of planar epithelial sheets two to three cell layers thick, were harvested and cultured ex ovo. Multicellular wounds were made and allowed to heal. We found that the closure rate of embryonic wounds displayed a two-phase behavior, with rapid constriction lasting about a minute, followed by more gradual contraction until the wound closed. Fluorescent staining revealed that soon after wounding a broad, faint ring of contractile actin and myosin-II encircles the wound. By one minute post wounding this structure gives way to a narrow actomyosin band at the wound border, consistent with a “purse string” healing mechanism observed in other embryonic systems. We hypothesize that contraction of the broad ring is responsible for the initial, rapid phase of wound closure, and that the narrow purse string drives the later slower phase. To test these mechanisms, we implemented both in a finite element computational model. We found that the rapid initial phase of wound closure is consistent only with an isotropic contraction of the broad ring surrounding the wound, and that the slower phase can be accounted for by the formation and circumferential contraction of fibers at the wound margin. Together, these two mechanisms can quantitatively reproduce the observed wound healing dynamics. The results of this integrated experimental and computational investigation suggest that a new mechanism, the isotropic contraction of cells in a broad ring around the wound, works together with an actomyosin contractile ring to close an embryonic wound.