Effects of Direct Current Electric Fields on Cell Migration and Actin Filament Distribution in Bovine Vascular Endothelial Cells

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.

Electrical Stimulation in Tissue Regeneration

“…EF may also alter ligand binding as result of the modification of the density and distribution of receptors through polarizing membrane components, moving receptors, or alternating receptor conformation. For instance, a DC EF adjusted the assembly and distribution of actin filaments within the cytoplasm of endothelial cells (Li & Kolega, 2002). As part of the complex intracellular signalling pathways, cytoskeleton provides structural stability and elasticity to the cell undergoing multiple deformations without losing its integrity.…”

Switching direction in electric-signal-induced cell migration by cyclic guanosine monophosphate and phosphatidylinositol signaling

“…For example, corneal rat epithelial cells, human keratinocytes, osteoblasts, rat prostate cancer cells, lymphocyte, and Xenopus neurons migrate toward the cathode, whereas corneal stromal fibroblasts, osteoclasts, human granulocyte, and macrophage migrate toward the anode. Even in the same cell type, cells derived from different species exhibit opposite migration direction in dcEFs; bovine vascular endothelial cells migrate toward the cathode, whereas human vascular endothelial cells migrate toward the anode (10,11). Furthermore, lens epithelial cells change their migration direction depending on the applied electric field strength (12).…”

Harnessing the Electric Spark of Life to Cure Skin Wounds

“…Several cell types that are implicated in wound repair increase their speed and direction of migration (electrotaxis) in response to an EF, as summarized in Table 1. 14,[19][20][21][22][23][24][25][26][27][28][29][30] Along with the antibacterial effect that EFs have shown in several studies, 3 cells involved in the immune response such as neutrophils, lymphocytes, and monocytes show cathodal migration (toward the wound center) in an EF. 14,19 Granulocytes migrate toward the anode at 2.5 mM Ca 2 + and toward the cathode at 0.1 mM Ca 2 + .…”

“…Endothelial cells respond to EFs by projecting broad, actin-filled lamellipodia. 24 Keratinocytes that are involved in the later stages of the wound repair process migrate cathodally on several matrices. 14,25,26 Fibroblasts, which are also implicated in later stages of wound repair, show voltage-and time-dependent electrotactic responses.…”