A Computational Model of Calcium Signals Around Laser-Induced Epithelial Wounds

Epithelial wounds heal in multiple stages that involve wound detection, cell migration, and cell proliferation. One of the earliest signals of wound detection is an increase in cytosolic calcium concentration. Laser-ablation wounds in Drosophila epithelia trigger complex calcium signaling dynamics on multiple spatiotemporal scales. Given multiple hypothesized mechanisms that may drive calcium signals, we have developed a computational model to test the plausibility of these hypotheses and further understand the underlying biology. The model consists of intracellular exchange of calcium between cytosol and endoplasmic reticulum (ER), as well as exchange of calcium and other ions with the extracellular space and neighboring cells. The model thus couples calcium concentrations and membrane potentials among gap-junction-connected epithelial cells. These ion exchanges are initiated in the model by microtears in the plasma membranes of cells near the wound and by the activation of G-protein coupled receptors via a wound-induced diffusible ligand. We will discuss the model in detail, evaluate the plausibility of its hypotheses , and describe its experimentally testable predictions.