Computational and experimental study of the mechanics of embryonic wound healing

Abstract

Wounds in the embryo show a remarkable ability to heal quickly without leaving a scar. Previous studies have found that an actomyosin ring (“purse string”) forms around the wound perimeter and contracts to close the wound over the course of several dozens of minutes. Here, we report experiments that reveal an even faster mechanism which remarkably closes wounds by more than 50% within the first 30 seconds. Circular and elliptical wounds (~100 µm in size) were made in the blastoderm of early chick embryos and allowed to heal, with wound area and shape characterized as functions of time. The closure rate displayed a biphasic behavior, with rapid constriction lasting about a minute, followed by a period of more gradual closure to complete healing. Fluorescent staining suggests that both healing phases are driven by actomyosin contraction, with relatively rapid contraction of fibers at cell borders within a relatively thick ring of tissue (several cells wide) around the wound followed by slower contraction of a thin supracellular actomyosin ring along the margin, consistent with a purse string mechanism. Finite-element modeling showed that this idea is biophysically plausible, with relatively isotropic contraction within the thick ring giving way to tangential contraction in the thin ring. In addition, consistent with experimental results, simulated elliptical wounds heal with little change in aspect ratio, and decreased membrane tension can cause these wounds to open briefly before going on to heal. These results provide new insight into the healing mechanism in embryonic epithelia.

Simple and accurate methods for quantifying deformation, disruption, and development in biological tissues

“…The DDE method succeeded in identifying the time course of straining, whereas XCOR revealed only noise (figure 6). For the circular punched wound, the first principal strain showed a contractile ring around the wound border, consistent with the isotropic contraction model [2] (figure 6a,d; electronic supplementary material, video 4). The SIMPLE algorithm detected a strain concentration around the wound consistent with localized isotropic contraction [2] (figure 6g and the electronic supplementary material, video 4).…”

“…The interplay of isotropic constriction, passive elastic recovery and stretching introduced during wound creation became apparent, providing insight into wound healing mechanisms and fetal surgery [2,27,28]. The strain fields associated with circular and elliptical ablated wounds …”

Growth and remodelling for profound circular wounds in skin

“…In Taber ( 2009 ), a general theory was developed describing the mechanical feedback to the growth rate during morphogenesis and was applied to the embryonic wound healing in the circular geometry with tension. Very recently, a computational model has been developed in Wyczalkowski et al ( 2013 ) considering both circular and elliptical geometries, with experiments, displaying a biphasic behaviour of the wound closure first promoted by the actomyosin isotropic contraction within a thick ring and later by a circumferential contraction within a thinner ring. However, for the mouse models, by the contraction of myofibroblasts which is responsible for 80 percents of the wound area reduction (Mawaki et al 2007 ), the initial circularity can be lost (Fig.…”

“…However, for the mouse models, by the contraction of myofibroblasts which is responsible for 80 percents of the wound area reduction (Mawaki et al 2007 ), the initial circularity can be lost (Fig. 1 a, b) compared to the embryonic wound healing (Wyczalkowski et al 2013 ).…”

Mechanical Forces in Cutaneous Wound Healing: Emerging Therapies to Minimize Scar Formation

“…As a result, three different phases in early chick embryo healing were proposed: (1) contraction of a thick actin cable of cells in the first *30 s to close the wound area by >50%, (2) formation and contraction of a thin actin cable at the wound edge to close the wound almost completely over several minutes, and (3) ''zipping'' of wound edges via filopodia. 31 In adult healing, fibroblasts convert to myofibroblasts to form contractile granulation tissue and keratinocytes migrate from the edges of the wound via lamellipodia to re-epithelize the wound bed. 32 Given that fetal wounds experience much lower resting stress and have a different mechanism of wound contraction, mechanical forces in the wound environment likely play a key role in scarless fetal wound healing.…”