Nematic cell alignment directs calcium waves in an epithelial monolayer

Tissues rely on supracellular signals to coordinate their cells over a long range. Two such tissue-scale cues are calcium waves and patterns of cell-cell alignment or nematic order. During wound healing, for example, calcium waves propagate across a tissue to guide directed cell migration and reepithelialization. Defects in long-range cell-cell alignment, or nematic orientation, can act to localize morphogenetic events in a tissue. Although these two cues have been considered in isolation, we demonstrate a relationship in epithelial tissue between long-range calcium signaling and the cell's nematic order: The speed of a wound-induced calcium wave depends on the angle between the wave vector and cell axis, with maximal wave speed occurring perpendicular to the tissue's orientation. Including anisotropic diffusive coupling between cells in a canonical reaction-diffusion model recapitulates our measured calcium wave dynamics. Our model demonstrates how orientation defects could desynchronize information propagation across a tissue. The anisotropic diffusivity in our model leads to a calcium wave front being bent around nematic defects. Therefore, cells the same distance from a wound can receive the calcium signal at different times. Our work elucidates how spatial patterns in global cell alignment can control collective communication via calcium signaling during development, wound healing, and disease.