Abstract
Sensing and responding to endogenous electrical fields are important abilities for cells engaged in processes such as embryogenesis, regeneration and wound healing. Many types of cultured cells have been induced to migrate directionally within electrical fields in vitro using a process known as galvanotaxis. The underlying mechanism by which cells sense electrical fields is unknown. In this study, we assembled a polydimethylsiloxane (PDMS) galvanotaxis system and found that mouse fibroblasts and human prostate cancer PC3 cells migrated to the cathode. By comparing the effects of a pulsed direct current, a constant direct current and an anion-exchange membrane on the directed migration of mouse fibroblasts, we found that these cells responded to the ionic flow in the electrical fields. Taken together, the observed effects of the calcium content of the medium, the function of the store-operated calcium channels (SOCs) and the intracellular calcium content on galvanotaxis indicated that calcium ionic flow from the anode to the cathode within the culture medium permeated the cells through SOCs at the drift velocity, promoting migration toward the cathode. The RTK-PI3K pathway was involved in this process, but the ROCK and MAPK pathways were not. PC3 cells and mouse fibroblasts utilized the same mechanism of galvanotaxis. Together, these results indicated that the signaling pathway responsible for cathode-directed cellular galvanotaxis involved calcium ionic flow from the anode to the cathode within the culture medium, which permeated the cells through SOCs, causing cytoskeletal reorganization via PI3K signaling.
Highlights
Endogenous direct-current electrical fields (EFs) are present in many organisms and play significant roles in a number of physiological processes, including embryonic development, regeneration, wound healing, and tumor invasion and metastasis [1, 2]
In the absence of an electrical field mouse fibroblasts and PC3 cells migrated in a random, non-directional manner
When a 5 V/cm electrical field was applied, the mouse fibroblasts and PC3 cells were strongly inclined to migrate in the direction of the cathode (S1 and S2 Movies)
Summary
Endogenous direct-current electrical fields (EFs) are present in many organisms and play significant roles in a number of physiological processes, including embryonic development, regeneration, wound healing, and tumor invasion and metastasis [1, 2]. The electrical fields in intact Xenopus embryos are generated by spatial differences in the transepithelial potentials, with currents exiting the blastopore at densities as high as 100μA/cm. The electrical fields in intact Xenopus embryos are generated by spatial differences in the transepithelial potentials, with currents exiting the blastopore at densities as high as 100μA/cm2 The sites where such currents exit the embryo are major regions of tissue reorganization, and disrupting the normal electrical current in an embryo can lead to developmental defects. The application of EFs at physiological strength induces many different types of cells to respond with directed migration [4]. These cells can move with directional preference toward the cathode or anode in electrical fields. Most cells migrate toward the cathode [5, 6], whereas a minority of cells migrate toward the anode [7, 8]
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