Mechanotransduction in Epithelia: “Sensing wounds in the force”
Epithelial wounding compromises tissue biomechanics by breaking the mechanical coherence between constituent cells. To understand epithelial wound repair we must therefore understand how cells sense and respond to changes in the mechanical properties of tissues. E-cadherin-based cell-cell junctions actively couple epithelial cells together into mechanically coherent populations. Further, mechanotransduction at junctions allows cells to sense local forces and elicit homeostatic responses to change. We now identify a novel junctional mechanotransduction pathway that coordinates collective cell responses to loss of tissue coherence during wounding. Using an UV-induced wound-healing model in epithelial cell monolayers we found that wounding elicits a collective response from neighbouring cells that extends several cell diameters from the wound itself. Increased junctional tension, through Myosin IIB, is a key element that drives this collective closure. Using FRET biosensors and inhibitors we identify junctional Src as responsible for coordinating this homeostatic response. Src is activated by acute reductions in junctional tension in the cells that will close the wound, through a pathway that involves interactions between E-cadherin and the protein tyrosine phosphatase PTPa. Thus a E-cadherin-based mechanotransduction pathway that is responsible for junctional tension homeostasis serves to mediate collective cellular responses during wound-healing.