Physics of Wound Healing: Investigating Calcium-Mediated Syncytia Formation

By studying the tissue-level response to wound healing in Drosophilae, whose cells divide regularly, we gain a foothold in understanding how other mitotically competent organisms (such as ourselves) will respond to wounds. In laser ablation wounds on the epithelium, we have seen that a cavitation bubble expands over the tissue and then recedes, stimulating a first wave of calcium signaling outside of the individual cells. Simultaneously, the cavitation bubble also causes small tears in the cell borders that are temporarily resealed. In the resealing process, scramblases flip phosphotidylserine (PS) from the inner layer to the outer layer. These openings also allow calcium to flow into the cell before they are sealed, which later causes a second calcium flash where the calcium passes from cell to cell via gap junctions. Calcium signaling activates actin dynamics, which propels regions of membrane into contact with each other. Regions of plasma membrane damage post-wound have been carefully mapped by the Hutson group at Vanderbilt, and they correlate strongly to regions where syncytia form. More investigation is needed to confirm whether calcium mediates the formation of syncytia as opposed to these processes simply being parallel to each other. By imaging the cell borders and calcium flash in real time via electron microscopy, I hope to determine if calcium plays an active role in the cell fusions that assist in wound healing, with followup gene knockdown experiments in order to confirm calcium triggers the formation of syncytia around the borders of a wound.