Modeling Intercellular MAPK Signaling in an Epithelial Wound Healing Assay

Recent experiments in epithelial wound healing 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 “rebounding wave” that originates immediately after injury, propagates deep into the cell layer, and then regresses back to the wound interface. The second MAPK wave is a slow developing, sustained wave that propagates from the wound interface. Experimentalists have suggested that the first wave is originated by reactive oxygen species (ROS) generated at the time of injury. We develop a mechanistic diffusion-convection model that produces the observed behavior by taking advantage of the coupling between ligand (e.g. EGF) and ROS species in the activation of the MAPK cascade. In our model, the second wave is initiated, and sustained by the stresses induced by the slow cell movement toward the injury. We explore the bi-stability of the model in connection with the bi-stability of the MAPK cascade. In particular, we look for traveling wave solutions of the model and their properties under various regimes.