Department of Physics, University of Maryland, College Park, United States; Institute for Physical Science and Technology, University of Maryland, College Park, United States
Yuchuan Miao
Department of Cell Biology, Johns Hopkins University, Baltimore, United States
Leonard J Campanello
Department of Physics, University of Maryland, College Park, United States; Institute for Physical Science and Technology, University of Maryland, College Park, United States
Matt J Hourwitz
Department of Chemistry & Biochemistry, University of Maryland, College Park, United States
Department of Cell Biology, Johns Hopkins University, Baltimore, United States
Abby L Bull
Department of Physics, University of Maryland, College Park, United States; Institute for Physical Science and Technology, University of Maryland, College Park, United States
Peter N Devreotes
Department of Cell Biology, Johns Hopkins University, Baltimore, United States
Institute for Physical Science and Technology, University of Maryland, College Park, United States; Department of Chemistry & Biochemistry, University of Maryland, College Park, United States
Department of Physics, University of Maryland, College Park, United States; Institute for Physical Science and Technology, University of Maryland, College Park, United States
Electrotaxis, the directional migration of cells in a constant electric field, is important in regeneration, development, and wound healing. Electrotaxis has a slower response and a smaller dynamic range than guidance by other cues, suggesting that the mechanism of electrotaxis shares both similarities and differences with chemical-gradient-sensing pathways. We examine a mechanism centered on the excitable system consisting of cortical waves of biochemical signals coupled to cytoskeletal reorganization, which has been implicated in random cell motility. We use electro-fused giant Dictyostelium discoideum cells to decouple waves from cell motion and employ nanotopographic surfaces to limit wave dimensions and lifetimes. We demonstrate that wave propagation in these cells is guided by electric fields. The wave area and lifetime gradually increase in the first 10 min after an electric field is turned on, leading to more abundant and wider protrusions in the cell region nearest the cathode. The wave directions display ‘U-turn’ behavior upon field reversal, and this switch occurs more quickly on nanotopography. Our results suggest that electric fields guide cells by controlling waves of signal transduction and cytoskeletal activity, which underlie cellular protrusions. Whereas surface receptor occupancy triggers both rapid activation and slower polarization of signaling pathways, electric fields appear to act primarily on polarization, explaining why cells respond to electric fields more slowly than to other guidance cues.
