Physical and Molecular Characterizations of Galvanotaxis and Its Implication in Glioblastoma

In order for the machineries within a living organisms to work properly, various types of signals must spatially and temporally orchestrate in harmony. However, aside from chemotaxis and action potentials, little is known about the physiological relevance of endogenous electric fields. These steady and long-lasting direct current electric fields (dcEFs) are fundamental in guiding cell migration, a phenomena termed galvanotaxis, and are shown to be involved in wound healing, embryogenesis, and even cancer metastasis. Utilizing photolithography, we have created a chip-based platform capable of monitoring cellular galvanotaxis in one-, two-, and three-dimensional settings. We found that galvanotaxis is a complex tug-of-war between mechanisms in favor of cathodic versus anodic response. We have also identified the novel roles of Syndecan-1, a membrane-bound heparan sulfate proteoglycan, in sensing and directing glioblastoma cells to migrate toward the cathode by localizing at the anodal face. This is the first direct evidence supporting the electrophoresis-based galvanotaxis model and provides valuable insights into the underlying mechanism. The pathological implications of galvanotaxis on the invasiveness of glioblastoma cells are also discussed