{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T18:34:07Z","timestamp":1786732447287,"version":"build-2736575974"},"reference-count":43,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T00:00:00Z","timestamp":1786665600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Khalifa University of Science and Technology","award":["FSU-2022-020"],"award-info":[{"award-number":["FSU-2022-020"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>\n                    The cell membrane potential (\n                    <jats:italic>V<\/jats:italic>\n                    <jats:sub>\n                      <jats:italic>m<\/jats:italic>\n                    <\/jats:sub>\n                    ) is of paramount significance in cell electrophysiology, most notably in excitable cells found in muscle and nervous tissues.\n                    <jats:italic>V<\/jats:italic>\n                    <jats:sub>\n                      <jats:italic>m<\/jats:italic>\n                    <\/jats:sub>\n                    is the voltage between the cell interior and extracellular space, and arises due to the diffusion potentials of potassium, chloride and sodium across the membrane. We recently reported a method to determine the resting membrane potential (RMP) of non-excitable cells including blood cells, chondrocytes, macrophages, and cancer cells, using a label-free, non-destructive, high-throughput method based on the electrical phenomenon\n                    <jats:italic>dielectrophoresis<\/jats:italic>\n                    (DEP). In this manuscript, we extend this technique to include the principal excitable cells, by altering the model to account for the different mechanisms which generate\n                    <jats:italic>V<\/jats:italic>\n                    <jats:sub>\n                      <jats:italic>m<\/jats:italic>\n                    <\/jats:sub>\n                    in these cells. Our results indicate that unlike the RMP in non-excitable cells, excitable cells may have a smaller potential measured across the membrane itself, with sizeable extracellular component of\n                    <jats:italic>V<\/jats:italic>\n                    <jats:sub>\n                      <jats:italic>m<\/jats:italic>\n                    <\/jats:sub>\n                    across the electrical double layer, measurable in the cell \u03b6-potential. When this was accounted for, the adapted model yielded results comparable to values in the literature. The model produced estimated values of RMP of \u221271.8 mV for SH-SY5Y neuroblastoma cells, and \u221274.2 mV in H9c2 cardiomyoblasts. Moreover, analysis of cardiomyoblasts in media with low concentrations of extracellular ions suggests that DEP can yield estimates of RMP in these media which align with published data for myocytes, with values of \u221254.1 mV between 100\u2013600 mSm\n                    <jats:sup>-1<\/jats:sup>\n                    and +12.7 mV below 100 mSm\n                    <jats:sup>-1<\/jats:sup>\n                    . This suggests that not only is DEP capable of accurate determination of\n                    <jats:italic>V<\/jats:italic>\n                    <jats:sub>\n                      <jats:italic>m<\/jats:italic>\n                    <\/jats:sub>\n                    across the full range of cell types, but also that it could be used to examine ion channel behaviour and its effect on\n                    <jats:italic>V<\/jats:italic>\n                    <jats:sub>\n                      <jats:italic>m<\/jats:italic>\n                    <\/jats:sub>\n                    across many ion concentrations.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0355723","type":"journal-article","created":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T17:56:23Z","timestamp":1786730183000},"page":"e0355723","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Dielectrophoretic estimation of resting membrane 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Sperelakis","year":"2011","edition":"4"},{"issue":"2","key":"pone.0355723.ref002","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1177\/0748730419836370","article-title":"Casein Kinase 1 Underlies Temperature Compensation of Circadian Rhythms in Human Red Blood Cells","volume":"34","author":"AD Beale","year":"2019","journal-title":"J Biol Rhythms"},{"issue":"1","key":"pone.0355723.ref003","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1002\/jcp.1041650121","article-title":"Changes in membrane potential during the progression of MCF-7 human mammary tumor cells through the cell cycle","volume":"165","author":"WF Wonderlin","year":"1995","journal-title":"J Cell Physiol"},{"issue":"6","key":"pone.0355723.ref004","doi-asserted-by":"crossref","first-page":"844","DOI":"10.1016\/j.bbalip.2014.09.010","article-title":"Phosphoinositides regulate ion channels","volume":"1851","author":"B Hille","year":"2015","journal-title":"Biochim Biophys 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giant axon during activity","volume":"22","author":"KS Cole","year":"1939","journal-title":"J Gen Physiol"},{"key":"pone.0355723.ref009","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1085\/jgp.27.1.37","article-title":"Potential, impedance, and rectification in membranes","volume":"27","author":"DE Goldman","year":"1943","journal-title":"J Gen Physiol"},{"key":"pone.0355723.ref010","doi-asserted-by":"crossref","DOI":"10.1007\/978-3-663-01627-4","volume-title":"Elektrobiologie: Die Lehre von den elektrischen Vorg\u00e4ngen im Organismus auf moderner Grundlage dargestellt","author":"J Bernstein","year":"1912"},{"key":"pone.0355723.ref011","doi-asserted-by":"crossref","first-page":"185","DOI":"10.3389\/fphys.2013.00185","article-title":"Membrane potential and cancer progression","volume":"4","author":"M Yang","year":"2013","journal-title":"Front Physiol"},{"key":"pone.0355723.ref012","first-page":"459","article-title":"Measuring resting membrane potential using the fluorescent 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using dielectrophoresis and flow cytometry","volume":"85","author":"FH Labeed","year":"2003","journal-title":"Biophys J"},{"issue":"1","key":"pone.0355723.ref020","doi-asserted-by":"crossref","first-page":"18477","DOI":"10.1038\/s41598-024-69000-7","article-title":"Label-free, non-contact determination of resting membrane potential using dielectrophoresis","volume":"14","author":"MP Hughes","year":"2024","journal-title":"Sci Rep"},{"issue":"1","key":"pone.0355723.ref021","doi-asserted-by":"crossref","first-page":"19446","DOI":"10.1038\/s41598-021-98102-9","article-title":"Vm-related extracellular potentials observed in red blood cells","volume":"11","author":"MP Hughes","year":"2021","journal-title":"Sci Rep"},{"issue":"11","key":"pone.0355723.ref022","doi-asserted-by":"crossref","first-page":"1200","DOI":"10.3390\/mi16111200","article-title":"The Multi-Conductivity Clausius-Mossotti Factor as an Electrophysiology Rosetta Stone: Dielectrophoresis, Membrane Potential and Zeta Potential","volume":"16","author":"MP Hughes","year":"2025","journal-title":"Micromachines (Basel)"},{"issue":"1","key":"pone.0355723.ref023","doi-asserted-by":"crossref","first-page":"15005","DOI":"10.1038\/s41598-022-19316-z","article-title":"Cytoplasmic anion\/cation imbalances applied across the membrane capacitance may form a significant component of the resting membrane potential of red blood cells","volume":"12","author":"MP Hughes","year":"2022","journal-title":"Sci Rep"},{"key":"pone.0355723.ref024","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1002\/elps.202200289","article-title":"The surface conductance of red blood cells and platelets is modulated by the cell membrane potential","volume":"44","author":"MP Hughes","year":"2023","journal-title":"Electrophoresis"},{"key":"pone.0355723.ref025","doi-asserted-by":"crossref","first-page":"569598","DOI":"10.3389\/fncel.2020.569598","article-title":"Electrophysiological Profile Remodeling via Selective Suppression of Voltage-Gated Currents by CLN1\/PPT1 Overexpression in Human Neuronal-Like Cells","volume":"14","author":"GC Demontis","year":"2020","journal-title":"Front Cell Neurosci"},{"issue":"1","key":"pone.0355723.ref026","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/s13024-017-0149-0","article-title":"The SH-SY5Y cell line in Parkinson\u2019s disease research: a systematic review","volume":"12","author":"H Xicoy","year":"2017","journal-title":"Molecular Neurodegeneration"},{"key":"pone.0355723.ref027","doi-asserted-by":"crossref","first-page":"19153","DOI":"10.1038\/s41598-019-55579-9","article-title":"Ten\u2013second electrophysiology: Evaluation of the 3DEP platform for high-speed, high-accuracy cell analysis","volume":"9","author":"KF Hoettges","year":"2019","journal-title":"Sci Rep"},{"key":"pone.0355723.ref028","doi-asserted-by":"crossref","first-page":"1562","DOI":"10.1002\/elps.202300202","article-title":"Electrical signature of heterogeneous human mesenchymal stem cells","volume":"45","author":"T Tsai","year":"2024","journal-title":"Electrophoresis"},{"issue":"2","key":"pone.0355723.ref029","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/0014-4827(74)90482-0","article-title":"Experimental and functional changes in transmembrane potential and zeta potential of single cultured cells","volume":"87","author":"K Redmann","year":"1974","journal-title":"Exp Cell Res"},{"issue":"1","key":"pone.0355723.ref030","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/0005-2736(76)90430-2","article-title":"Change in zeta potential and membrane potential of slime mold Physarum polycephalum in response to chemical stimuli","volume":"426","author":"M Hato","year":"1976","journal-title":"Biochim Biophys Acta"},{"key":"pone.0355723.ref031","doi-asserted-by":"crossref","first-page":"22475","DOI":"10.1038\/s41598-025-06371-5","article-title":"Vm and \u03b6-potential of Candida albicans correlate with biofilm formation","volume":"15","author":"MP Johnson","year":"2025","journal-title":"Sci Rep"},{"key":"pone.0355723.ref032","doi-asserted-by":"crossref","first-page":"055701","DOI":"10.1088\/1361-6501\/ad25de","article-title":"Rapid, label-free, contactless measurement of membrane potential in excitable H9c2 cardiomyoblasts using \u03b6-potential","volume":"35","author":"S Chacar","year":"2024","journal-title":"Meas Sci Technol"},{"issue":"1","key":"pone.0355723.ref033","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1113\/jphysiol.1959.sp006278","article-title":"The influence of potassium and chloride ions on the membrane potential of single muscle fibres","volume":"148","author":"AL Hodgkin","year":"1959","journal-title":"J Physiol"},{"key":"pone.0355723.ref034","volume-title":"Cell Physiology Sourcebook","author":"N Sperelakis","year":"2011","edition":"4"},{"key":"pone.0355723.ref035","volume-title":"Fundamentals of Interface and Colloid Science","author":"J Lyklema","year":"1991"},{"issue":"3","key":"pone.0355723.ref036","doi-asserted-by":"crossref","first-page":"1493","DOI":"10.1152\/physrev.00047.2017","article-title":"CLC Chloride Channels and Transporters: Structure, Function, Physiology, and Disease","volume":"98","author":"TJ Jentsch","year":"2018","journal-title":"Physiol Rev"},{"key":"pone.0355723.ref037","doi-asserted-by":"crossref","first-page":"151","DOI":"10.3389\/fphar.2017.00151","article-title":"ClC Channels and Transporters: Structure, Physiological Functions, and Implications in Human Chloride Channelopathies","volume":"8","author":"DR Poroca","year":"2017","journal-title":"Front Pharmacol"},{"issue":"6","key":"pone.0355723.ref038","doi-asserted-by":"crossref","first-page":"1077","DOI":"10.1085\/jgp.95.6.1077","article-title":"Chloride current in mammalian cardiac myocytes. Novel mechanism for autonomic regulation of action potential duration and resting membrane potential","volume":"95","author":"RD Harvey","year":"1990","journal-title":"J Gen Physiol"},{"issue":"1","key":"pone.0355723.ref039","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/S0008-6363(98)00173-4","article-title":"Role of cardiac chloride currents in changes in action potential characteristics and arrhythmias","volume":"40","author":"M Hiraoka","year":"1998","journal-title":"Cardiovasc Res"},{"key":"pone.0355723.ref040","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.pharmthera.2014.08.002","article-title":"Potential role of cardiac chloride channels and transporters as novel therapeutic targets","volume":"145","author":"GB Adkins","year":"2015","journal-title":"Pharmacol Ther"},{"key":"pone.0355723.ref041","doi-asserted-by":"crossref","first-page":"2075","DOI":"10.1038\/s41598-017-02129-w","article-title":"Kv3.4 is modulated by HIF-1\u03b1 to protect SH-SY5Y cells against oxidative stress-induced neural cell death","volume":"7","author":"MS Song","year":"2017","journal-title":"Sci Rep"},{"key":"pone.0355723.ref042","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/j.neuroscience.2021.10.033","article-title":"Changes in Biophysical Properties of Undifferentiated SH-SY5Y Cells During Long-term Cultures","volume":"482","author":"S Santillo","year":"2022","journal-title":"Neuroscience"},{"key":"pone.0355723.ref043","volume-title":"The Art of Electronics","author":"P Horowitz","year":"2015","edition":"3"}],"container-title":["PLOS One"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0355723","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T17:56:31Z","timestamp":1786730191000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0355723"}},"subtitle":[],"editor":[{"given":"Daniel Ioan","family":"Hunyadi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,8,14]]},"references-count":43,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2026,8,14]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0355723","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,14]]}}}