Electric signalling controls wound healing, cell proliferation and division, and nerve regeneration
In this project we designed four different level of electrotaxis experiment from in vitro and in vivo, from single cell monolayer cells then further to stratified multiple layers of cells, to prove that cell directional migration, wound healing and nerve regeneration are all controlled by endogenous electric field. Using single cell model and monolayer scratch wound model in vitro, we demonstrated the electrotactic response of directional cell migration and wound healing were all controlled by physiological EF. Using a three dimensional stratified cornea epithelium wound model ex vivo, we further proved that electric signals could modulate the directional cell migration in a wound. We then used an in vivo rat corneal model, which generates its own endogenous EF, to show that the direction of nerve growth, the rate of epithelial wound healing and the orientation of the cell division in wound healing were all controlled by the wound-induced engenous EF. Wounding the cornea generates endogenous EFs in the plane of the epithelial sheet because the transcorneal potential difference (TCPD); +40mb internally positive) collapses at the wound edge, but is maintained at normal levels 0.5 mm back from the wound. We manipulated the endogenous EF this creates using clinically proved drugs with differing actions. The wound-induced EF controlled the orientation of cell division; most epithelial cells divided with a cleavage plane parallel to the wound edge and perpendicular to the EF vector. Increasing or decreasing the EF pharmacological, respectively increased or decreased the extent of oriented cell division. IN addition, cells closest to the wound edge where the EF was highest, were oriented most strongly by the EF. Remarkably, an endogenous EF also enhanced the frequency of cell division. This also was regulated by enhancing or suppressing the EF pharmacologically. Since the endogenous EF also regulated the wound healing rate, it may act as one control of the interplay between cell migration and cell division during healing.