Competing signaling pathways controls electrotaxis

Understanding how cells follow exogenous cues is a key question for biology, medicine, and bioengineering. Growing evidence shows that electric fields represent a precise and programmable method to control cell migration. Most data suggest that the polarization of membrane proteins and the following downstream signaling are central to electrotaxis. Unfortunately, how these multiple mechanisms coordinate with the motile machinery of the cell is still poorly understood. Here, we develop a mechanistic model that explains electrotaxis across different cell types. Using the zebrafish proteome, we identify membrane proteins directly related to migration signaling pathways that polarize anodally and cathodally. Further, we show that the simultaneous and asymmetric distribution of these membrane receptors establish multiple cooperative and competing stimuli for directing the anodal and cathodal migration of the cell. Using electric fields, we enhance, cancel, or switch directed cell migration, with clear implications in promoting tissue regeneration or arresting tumor progression.