Cellular integration of physical and biochemical damage signals in the generation of tissue-level wound responses

Laser wounds in Drosophila epithelia trigger calcium signaling – an early and conserved sign of wound detection – that includes an initial calcium influx into damaged cells within 0.1 s, a first expansion into adjacent cells over ~20 s, and a delayed second expansion to a much larger set of surrounding cells between 40-300 s. We have developed a computational model to test the plausibility of multiple hypothesized mechanisms driving these calcium signals and to further understand the underlying biology. The model includes calcium currents between each cell’s cytosol and its endoplasmic reticulum (ER), the extracellular space, and neighboring cells. These calcium currents are initiated in the model by cavitation-induced microtears in the plasma membranes of cells near the wound (initial influx), flow through gap junctions into adjacent cells (first expansion), and by the activation of G-protein coupled receptors via a wound-induced diffusible ligand (second expansion). The production, processing and propagation of the ligand is modeled using reaction-diffusion equations on a continuous, two-dimensional space. We will discuss how the model matches experimental observations and makes experimentally testable predictions.