A mathematical model of intercellular signaling during epithelial wound healing

Abstract

Recent experiments monitoring the healing process of wounded epithelial monolayers have demonstrated the necessity of MAPK activation for coordinated cell movement after damage. This MAPK activity is characterized by two wave-like phenomena. One MAPK “wave” that originates immediately after injury, propagates deep into the cell sheet, away from the edge, and then rebounds back to the wound interface. After this initial MAPK activity has largely disappeared, a second MAPK front propagates slowly from the wound interface and also continues into the cell sheet, maintaining a sustained level of MAPK activity throughout the cell sheet. It has been suggested that the first wave is initiated by Reactive Oxygen Species (ROS) generated at the time of injury. In this work, we develop a minimal mathematical model that reproduces the observed behavior. The main ingredients of our model are a competition between ligand (e.g., Epithelial Growth Factor) and ROS for the activation of Epithelial Growth Factor Receptor, and a feedback loop between receptor occupancy and MAPK activation. We explore the mathematical properties of the model and look for traveling wave solutions consistent with the experimentally observed MAPK activity patterns.