Publication date: 25th July 2016
The closure of gaps within epithelia is crucial to maintain the integrity and the homeostasis of the tissue during wound healing or cell extrusion processes. Cells mediate gap closure through either the assembly of multicellular actin-based contractile cables (purse-string contraction) or the protrusive activity of border cells into the gap (cell crawling). I will present experimental data and numerical modeling that show how these mechanisms can mutually interact to promote efficient epithelial gap closure and how mechanical constraints can regulate these mechanisms.I will first present how geometrical constraints dictate mechanisms of epithelial gap closure. We determine the importance of tissue shape during closure and the role of curvature of cell boundaries in this process. An essential difference between the two closure mechanisms is that cell crawling always pulls the edge of the tissue forward (i.e. towards the gap) while purse string pulls the edge forward or backwards depending on the local geometry. Our study demonstrates how the interplay between these two mechanisms is crucial for closing gaps and wounds, which naturally come in arbitrary shapes. Along this line, cells at convex edges (positive curvature) adopt the crawling mechanism whereas the ones at concave edges (negative curvature) prefer the purse-string mechanism. Sensing such large-scale curvatures are beyond the capability of molecular curvature sensors and must involve larger scale cellular structures. I will show how sub-cellular mechanism driven by differential actin dynamical behaviors can serve as large-scale curvature sensors. Active directional flow in response to geometrical tension anisotropy help cells to differentiate between positive and negative curvatures and switch between two migration mechanisms accordingly.
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