Vertex Model of Wound Healing Mechanics in Drosophila Epithelia

Microscopic wounds in Drosophila epithelia drive complex and tissue-wide mechanical changes. These changes are necessary for wound healing, but they must be reversed soon after completion to restore an epithelium’s normal state. To understand how the tissue dynamically alters its mechanics, we combine in vivo genetic manipulations, laser wounding, and computational vertex models. In one combination, fitting the vertex model to in-vivo cell ablation experiments reveals that the epithelium’s mechanics are poised near a phase change in parameter space, allowing modulation of tissue fluidity via small changes in cell contractility. In the same set of experiments, we use localized RNAi knockdown of the signaling protein rho kinase (Rok) to reduce cell contractility across half the epithelium. The vertex model reveals that the decrease in cellular tension throughout the knockdown domain can be compensated for by a small area strain – yielding one continuous epithelium with visually similar regions that nonetheless have significantly different mechanical properties. This exotic equilibrium state creates adjacent control and experimental domains, which are useful for investigating how epithelial tension affects cellular responses to wounding. In another set of coupled experiments and models, we observed that wound-induced cell-cell fusion promotes rapid wound closure. Using the vertex model, we test the hypothesis that fusions effectively rearrange cells without energetically costly intercalations, maintaining the tissue’s fluid phase against strain which would normally induce a return to the tissue’s solid phase. The coupling of modeling and experiment enriches theory and is critical in understanding in vivo mechanics.