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Abstract
Electric fields exceeding 1 V/cm occur during wound healing, morphogenesis, and tumor
growth, and such fields have been shown to induce directional migration of a variety
of different cells. However, the mechanism by which electric fields direct cell movement
is not yet understood, and the effects on vascular endothelial cells are entirely
unknown. We demonstrate that cultured bovine aortic endothelial cells migrate toward
the cathode of an applied electric field. Time-lapse microscopic imaging shows that
the field suppresses protrusive activity from anode-facing surfaces of the cells while
stimulating protrusions from surfaces that face the cathode. The threshold for this
response is 1–2 V/cm, similar to field strengths measured in vivo. In addition, fluorescence
microscopy shows that lamellipodia projecting toward the cathode are rich in actin
filaments. Using quantitative image analysis, we show that the electric field induces
a transient 80% increase in the amount of filamentous actin in the cell. Comparison
of the distribution of F-actin with total protein distribution indicates that F-actin
is asymmetrically distributed in the cytoplasm, being selectively enriched toward
the cathode. We propose that physiological electric fields direct cell migration by
eliciting an intracellular signal that creates new sites for actin assembly in the
cathodal cytoplasm.