Cell Migration in Weak Electric Fields: Molecular and Functional Analysis of Different Mammalian Cell Species

It is increasingly recognized that weak electric fields provide directional clues that guide migrating cells to well-defined places in multicellular organisms. Wound healing is a major example for such a process in which an electrical potential gradient towards the centre of the wound directs cells from the periphery to close the lesion. It was shown recently that the healing rate of wounded rat cornea can be regulated by enhancing or suppressing the endogenous electric field pharmacologically. In a related manner it is possible to induce migration or reorientation by applying physiological electric fields to single cells or cell monolayers derived from different tissues and species. Myoblasts and endothelial cells, for example, realign their long axes perpendicular to the electric field. The amoebae Dictyostelium discoideum shows strong directional migration if stimulated by relative strong electric fields. Due to the enormous physiological importance, the influence of small electric fields on the migration of single cells and cell monolayers has been investigated intensively in vitro in order to understand the underlying principles. Nevertheless several aspects of the so-called electrotaxis have not been clarified, as not all types of cell start to migrate at the same electric field strength or in the same direction. Since very few studies have addressed the differences between cells originating from different tissues in particular with respect to their individual cell-cell and cell-substrate contacts, this project will investigate the possible impact of these cell junctions on cell migration. The project will furthermore address whether cells of a certain tissue show different migration characteristics as single cells compared to an ensemble of these cells, like in a cell monolayer. Finally we would like to study whether weak electric fields increase the inherent motility in confluent monolayers of cells in which no lateral movement is possible due to the non-existence of open spaces.