Ionic (electric) cell-cell signaling during wound healing

Cell extrusion is an essential process to repel mutated and damaged cells to gain tissue homeostasis in epithelial tissue. While the processes at the interface between an extruding cell and its neighbors, characterized by pulse-string and lamellipodial interactions, are well-understood, the mechanisms extending beyond the single-cell level—particularly in scenarios not governed by contact proximity—remain elusive. Here, we report that the epithelial system raises the tissue-scale grand movements to overcome the complexity of problems when the local damage becomes no longer single, but multiple and distant from each other using micro-patterned laser irradiation. The consequence is that multi-point damages merged become one spot caused by bulk elastic behaviors modulating its motion inward and outward collectively. We elucidated that those collective behaviors of the epithelial system were modulated by radial propagation of bioelectrical signals from a wound. We found the mechanosensitive calcium channels control the gradients of the bioelectric signal and frequency of the excitability, suggesting the cellular bioelectric signal is essential to drive the long-range collective extrusion of the epithelial systems.