Electromigration of Cell Surface Macromolecules during Galvanotaxis

Abstract

Weak, DC electric fields (EFs) direct cellular polarity, migration and outgrowth. They are used to induce polarity during tissue engineering and direct migration to promote epidermal wound repair. Fields as weak as 10 mV/mm, are sufficient to direct migration, although the mechanisms used by cells to sense such weak fields are still debated as weaknesses exist in the competing models. We hypothesize that cellular polarization is achieved by the redistribution of a cell surface, electric field receptor (EFR) in the presence of an applied EF. We are investigating the electromigration model that depends on electrically generated forces in the plane of the plasma membrane and parallel to the electric field vector, specifically, electrophoretic and electro-osmotic forces. Electrophoretic force drives net negatively charged macromolecules to the anode while electro-osmotic flow of water, in the boundary layer, drives macromolecules with large extracellular domains to the cathode. We have derived a model based on these opposing forces, to predict the relative concentration of surface proteins over space and time, allowing us to test the redistribution of known plasma membrane surface macromolecules in applied EFs and under controlled conditions. The model closely describes accumulation of a net negatively charged, GPI-anchored, fluorescent protein to the cathode under different field strengths, showing that redistribution reaches steady-state within minutes, significantly faster than cathodally migrating cells turn toward the cathode. The model is useful for determining the most likely candidates for the EFR on many different cell types.