Current Biology
Volume 23, Issue 7, 8 April 2013, Pages 560-568
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Article
Electrophoresis of Cellular Membrane Components Creates the Directional Cue Guiding Keratocyte Galvanotaxis

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Summary

Background

Motile cells exposed to an external direct current electric field will reorient and migrate along the direction of the electric potential in a process known as galvanotaxis. The underlying physical mechanism that allows a cell to sense an electric field is unknown, although several plausible hypotheses have been proposed. In this work we evaluate the validity of each of these mechanisms.

Results

We find that the directional motile response of fish epidermal cells to the cathode in an electric field does not require extracellular sodium or potassium, is insensitive to membrane potential, and is also insensitive to perturbation of calcium, sodium, hydrogen, or chloride ion transport across the plasma membrane. Cells migrate in the direction of applied forces from laminar fluid flow, but reversal of electro-osmotic flow did not affect the galvanotactic response. Galvanotaxis fails when extracellular pH is below 6, suggesting that the effective charge of membrane components might be a crucial factor. Slowing the migration of membrane components with an increase in aqueous viscosity slows the kinetics of the galvanotactic response. In addition, inhibition of PI3K reverses the cell’s response to the anode, suggesting the existence of multiple signaling pathways downstream of the galvanotactic signal.

Conclusions

Our results are most consistent with the hypothesis that electrophoretic redistribution of membrane components of the motile cell is the primary physical mechanism for motile cells to sense an electric field. This chemical polarization of the cellular membrane is then transduced by intracellular signaling pathways canonical to chemotaxis to dictate the cell’s direction of travel.

Highlights

► We find no evidence of asymmetric ion flow into the cell as the galvanotactic sensor ► Cells move in the direction of fluid flow, but this is not required in galvanotaxis ► The charge and mobility of membrane components are critical to galvanotaxis ► A PI3K-dependent pathway exists that transduces this polarization to the cytoskeleton

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