Electrical stimulation directs articular chondrocyte and chondrosarcoma migration in a 3D collagen matrix

Electrical signals are fundamental regulators of cell migration and growing numbers of studies have demonstrated electrically guided cancer cell migration. Chondrosarcomas, cartilage forming tumors, are highly metastatic and resistant to chemo and radiation therapies. To measure cellular migration in a three-dimensional (3D) environment a device was 3D-printed to house a collagen gel with embedded cells while enabling direct current electric field (DC-EF) application. Articular chondrocytes and chondrosarcoma cells were exposed to a 1 V/cm electric field for a duration of 12 h while tracking their migration behavior. We observed that both cell types migrated towards the anode while chondrosarcoma cells showed a stronger directional response. We observed an EF-induced shift from diffusive migration trajectories towards ballistic migration behavior in articular chondrocytes and directed 'wobble' migration in chondrosarcoma. In articular chondrocytes we observed significant increases in the length of protrusions directed towards the anode (p < 0.05), as opposed to cathode directed protrusions after EF-exposure. Notably chondrosarcoma cells exhibited tiny protrusions of less than a few microns in length which sporadically extruded and retracted. Chondrosarcoma cells were loaded with FluoVolt to track real-time changes in membrane potential. Cells exposed to a 1V/cm electric field for 30 s showed a dynamic cell membrane hyperpolarization and repolarization during EF-exposure with a maximum hyperpolarization approximated to be on the order of -5 mV. To our knowledge, these are the first descriptions of the effects of electrical fields on directional cell migration in a 3D environment.