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* Laboratory of Immunology and Vascular Biology, Department of Pathology, School of Medicine, and
Department of Mechanical Engineering, Stanford University, Stanford, CA 94305; and
Center for Molecular Biology and Medicine, Veterans Affairs Palo Alto Health Care System, Palo Alto, CA 94304
Electric fields are generated in vivo in a variety of physiologic and pathologic settings, including penetrating injury to epithelial barriers. An applied electric field with strength within the physiologic range can induce directional cell migration (i.e., electrotaxis) of epithelial cells, endothelial cells, fibroblasts, and neutrophils suggesting a potential role in cell positioning during wound healing. In the present study, we investigated the ability of lymphocytes to respond to applied direct current (DC) electric fields. Using a modified Transwell assay and a simple microfluidic device, we show that human PBLs migrate toward the cathode in physiologically relevant DC electric fields. Additionally, electrical stimulation activates intracellular kinase signaling pathways shared with chemotactic stimuli. Finally, video microscopic tracing of GFP-tagged immunocytes in the skin of mouse ears reveals that motile cutaneous T cells actively migrate toward the cathode of an applied DC electric field. Lymphocyte positioning within tissues can thus be manipulated by externally applied electric fields, and may be influenced by endogenous electrical potential gradients as well.
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1 This work is supported by Postdoctoral Training Grant 5T32AI07290-20 from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, to the Immunology Program, Stanford University and a grant from the Stanford Bio-X Interdisciplinary Initiative Program (to F.L.). F.B., E.C.B., and J.G.S. are also supported by a grant from the Stanford Bio-X Interdisciplinary Initiative Program. This work is also supported by Grant R03DK069395 from the National Institutes of Health (to T.S.). This study is supported in part by grants from the National Institutes of Health (to E.C.B. and J.G.S.), and an award from the Department of Veterans Affairs (to E.C.B.).
2 F.L. and F.B. contributed equally to this work.
3 Address correspondence and reprint requests to Dr. Francis Lin and Dr. Eugene C. Butcher, Laboratory of Immunology and Vascular Biology, Department of Pathology, School of Medicine, Stanford University, Stanford, CA 94305. E-mail addresses: flin2{at}stanford.edu and ebutcher{at}stanford.edu
4 Abbreviations used in this paper: DC, direct current; EI, electrotactic index.
5 The online version of this article contains supplemental material.
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