OptoCPM: Modeling OptoEGFR-Induced Directed Collective Cell Migration in MCF10A Cells

Abstract

Directed collective cell migration is essential for processes like wound healing, development, and cancer invasion. Signaling through the epidermal growth factor receptor (EGFR) and its downstream effector extracellular signal-regulated kinase (ERK) have been shown to drive such migration through spatially organized waves of activity. However, the mechanistic link between localized patterns of EGFR activity and collective cell migration remains unclear. One recent advance has been the application of optogenetic EGFR systems to drive collective cell migration at a tissue scale, where patterns of EGFR activity can be directly controlled with light. Here, we develop and validate the first cellular Potts model (CPM) with an optogenetic input layer to simulate directed collective migration in MCF10A cells in response to static and dynamic optogenetic stimulation. We then use this model to propose that EGFR activation wave speed and tissue geometry are key physical factors influencing direction of tissue migration, and that EGFR activation waves induce tissue migration via different physical mechanisms in different commonly used cell migration model systems. This work contributes an optogenetic CPM tuned for MCF10A cells to complement in vitro cell migration research, and we hope for its use to inform the development of novel therapeutic applications that involve breaches, overgrowth, or altogether abnormal behavior of the human epithelium.