The interplay of membrane potential and cytoskeleton directs cell migration

The cell membrane potential is a crucial regulator of electrical activities in excitable cells such as neurons and heart cells. Recently, its significance has been observed in non-excitable cells, including epithelial cells. This potential is generated by specific ion channels and transporters with distinct ion selectivity and permeability. Intriguingly, recent research has demonstrated a noteworthy membrane hyperpolarization in metastatic breast cancer cell lines, MDA-MB-231 and MDA-MB-468, which is associated with enhanced invasion in vitro and metastasis in vivo. This hyperpolarization induces changes in cell morphology and dynamic cytoskeletal alterations, both essential for cell migration and invasion. However, the intricate interplay between membrane potential and the cytoskeleton in regulating cell migration remains enigmatic. In this study, we employ the genetically encoded voltage indicator Jedi2p-CYOFP to monitor voltage dynamics, alongside a membrane-proximal F-actin (MPA) reporter to assess local changes in MPA density. By tracking these parameters during cell migration, we investigate the alterations in membrane potential and MPA density. Our findings shed light on the potential relationship between MPA density and voltage dynamics at both the leading and trailing edges of migrating cells, offering valuable insights into the mechanisms governing cell migration. This work advances our understanding of the role of cell membrane potential and cytoskeletal dynamics in cancer metastasis and may pave the way for future therapeutic interventions targeting these pathways.