Direct Current Electric Fields Induce Collective Migration of Human Corneal Epithelial Monolayers

Abstract

Bioelectricity is an endogenous biological electric field (EF) that can be measured in vivo. A biological direct current (DC) EF is produced by ion fluctuations, and is a common response to wounds in various tissues. Our lab previously illustrated DC EF responses in corneal wounds in rodent models in vivo and in human corneal epithelial cell (hCEC) culture. We have observed that both endogenous DC EF and applied exogenous DC EF are capable of guiding cell migration in the process of electrotaxis. However, we have yet to examine exogenous DC EF responses in epithelial monolayers, which are more representative of a wound edge. Our aim was to characterize collective migration of epithelial monolayers to model electrotaxis of a wound edge. We hypothesized that exogenous DC EF can improve collective migration in hCEC monolayers, and therefore DC EF might be applicable for medical treatments of corneal wounds. To test the first part of this hypothesis, we applied exogenous DC EF to hCEC monolayers. We used a standard method of cell tracking combined with an advanced method of particle image velocimetry (PIV) analysis to extrapolate collective migration data. We observed that applications of DC EF to hCEC monolayers induced collective migration and directionality ‐ the directional precision of migration parallel to the EF. Increasing DC EF voltages of 0, 50, and 200 mV/mm2 positively correlated with increasing migration rates. In controls (0 mV/mm2), we observed no directionality, but at DC EF voltages of 50 and 200 mV/mm2 we observed a comparable directionality response, guiding cell migration parallel (0 degrees) to the DC EF. Further, directionality was promptly reversed following DC EF reversals (180 degrees). We concluded that DC EF provides a precise guidance signal for hCEC monolayers that might be applicable for corneal wound healing therapies. Future investigations will aim to dissect cellular mechanisms of the collective migration response to DC EF and to examine the feasibility of DC EF applications to corneal wounds in vivo.Support or Funding InformationNIH, NEI ‐ 2R01EY019101‐05A1 to MZ; DOD, MURI ‐ FA9550‐16‐1‐0052 to WL and MZThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.