{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T06:13:16Z","timestamp":1789020796744,"version":"build-2803163510"},"reference-count":95,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2021,5,10]],"date-time":"2021-05-10T00:00:00Z","timestamp":1620604800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>The biological impact of exogenous, alternating electric fields (AEFs) and direct-current electric fields has a long history of study, ranging from effects on embryonic development to influences on wound healing. In this article, we focus on the application of electric fields for the treatment of cancers. In particular, we outline the clinical impact of tumor treating fields (TTFields), a form of AEFs, on the treatment of cancers such as glioblastoma and mesothelioma. We provide an overview of the standard mechanism of action of TTFields, namely, the capability for AEFs (e.g., TTFields) to disrupt the formation and segregation of the mitotic spindle in actively dividing cells. Though this standard mechanism explains a large part of TTFields\u2019 action, it is by no means complete. The standard theory does not account for exogenously applied AEFs\u2019 influence directly upon DNA nor upon their capacity to alter the functionality and permeability of cancer cell membranes. This review summarizes the current literature to provide a more comprehensive understanding of AEFs\u2019 actions on cell membranes. It gives an overview of three mechanistic models that may explain the more recent observations into AEFs\u2019 effects: the voltage-gated ion channel, bioelectrorheological, and electroporation models. Inconsistencies were noted in both effective frequency range and field strength between TTFields versus all three proposed models. We addressed these discrepancies through theoretical investigations into the inhomogeneities of electric fields on cellular membranes as a function of disease state, external microenvironment, and tissue or cellular organization. Lastly, future experimental strategies to validate these findings are outlined. Clinical benefits are inevitably forthcoming.<\/jats:p>","DOI":"10.3390\/cancers13092283","type":"journal-article","created":{"date-parts":[[2021,5,10]],"date-time":"2021-05-10T10:49:51Z","timestamp":1620643791000},"page":"2283","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":71,"title":["Permeabilizing Cell Membranes with Electric Fields"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4411-5251","authenticated-orcid":false,"given":"Alondra A.","family":"Aguilar","sequence":"first","affiliation":[{"name":"Molecular Imaging Program at Stanford, Department of Radiology, Stanford University School of Medicine, Stanford, CA 94305, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1659-7991","authenticated-orcid":false,"given":"Michelle C.","family":"Ho","sequence":"additional","affiliation":[{"name":"Molecular Imaging Program at Stanford, Department of Radiology, Stanford University School of Medicine, Stanford, CA 94305, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5672-0520","authenticated-orcid":false,"given":"Edwin","family":"Chang","sequence":"additional","affiliation":[{"name":"Molecular Imaging Program at Stanford, Department of Radiology, Stanford University School of Medicine, Stanford, CA 94305, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2101-3567","authenticated-orcid":false,"given":"Kristen W.","family":"Carlson","sequence":"additional","affiliation":[{"name":"Beth Israel Deaconess Medical Center, Department of Neurosurgery, Harvard Medical School, Boston, MA 02215, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9958-2623","authenticated-orcid":false,"given":"Arutselvan","family":"Natarajan","sequence":"additional","affiliation":[{"name":"Molecular Imaging Program at Stanford, Department of Radiology, Stanford University School of Medicine, Stanford, CA 94305, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tal","family":"Marciano","sequence":"additional","affiliation":[{"name":"Novocure, Ltd., 31905 Haifa, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ze\u2019ev","family":"Bomzon","sequence":"additional","affiliation":[{"name":"Novocure, Ltd., 31905 Haifa, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0787-0634","authenticated-orcid":false,"given":"Chirag B.","family":"Patel","sequence":"additional","affiliation":[{"name":"Molecular Imaging Program at Stanford, Department of Radiology, Stanford University School of Medicine, Stanford, CA 94305, USA"},{"name":"Department of Neurology &amp; Neurological Sciences, Division of Neuro-Oncology, Stanford University School of Medicine, Stanford, CA 94305, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,5,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1016\/S0361-9230(98)00023-9","article-title":"Medicine and science in the life of Luigi Galvani (1737\u20131798)","volume":"46","author":"Bresadola","year":"1998","journal-title":"Brain Res. 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