Three-Dimensional Mechanical Cooperativity Optimises Epithelial Wound Healing

Abstract

Epithelial tissues serve as critical physical barriers that protect organs, making efficient repair essential upon damage. To achieve this, tissues must quickly react, forcing cells to rearrange and accommodate. Therefore, cells must cope with forces that will deform their shape to achieve these sudden but necessary changes. In the Drosophila wing disc, we showed how tissue fluidisation accelerated wound healing in 2D. However, the 3D aspect of tissue repair remains poorly understood. Here, we uncover a new mechanism aiding the tissue in repairing itself by changing cell height. We find actomyosin contractile cables at the wound edge connecting the apical and basal cell surface, which indent the apical side of the tissue and deform the basement membrane (BM), respectively. To understand the role of the different repair mechanisms, we developed a 3D vertex model allowing apico-basal intercalations. The model predicts that lateral cables play a role in regulating cell-cell intercalations, confirmed by Drosophila mutations affecting cell deformations. Our results demonstrate that lateral cables cooperate with the apical purse string to drive 3D cell shape changes and intercalations to promote more efficient wound repair.