{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T12:13:56Z","timestamp":1785413636865,"version":"3.56.0"},"reference-count":43,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T00:00:00Z","timestamp":1785196800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004070","name":"Khalifa University of Science and Technology","doi-asserted-by":"publisher","award":["RC2-2018-022"],"award-info":[{"award-number":["RC2-2018-022"]}],"id":[{"id":"10.13039\/501100004070","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004070","name":"Khalifa University of Science and Technology","doi-asserted-by":"publisher","award":["FSU-2022-020"],"award-info":[{"award-number":["FSU-2022-020"]}],"id":[{"id":"10.13039\/501100004070","id-type":"DOI","asserted-by":"publisher"}]},{"award":["RC2-2018-022"],"award-info":[{"award-number":["RC2-2018-022"]}],"id":[{"id":"https:\/\/ror.org\/05hffr360","id-type":"ROR","asserted-by":"publisher"}]},{"award":["FSU-2022-020"],"award-info":[{"award-number":["FSU-2022-020"]}],"id":[{"id":"https:\/\/ror.org\/05hffr360","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Biotechnology Center at Khalifa University"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Micromachines"],"abstract":"<jats:p>To survive, cells are able to adapt to a wide range of adverse conditions, such as varying pH from optimal (~7.4). They do this through mechanisms including acid-sensing ion channels, which alter cytosolic ion content and thus the cell\u2019s electrophysiological profile. However, the impact of this adaptation on cellular electrophysiology remains unexplored. We investigated the effects of culture at a range of extracellular pH on the electrophysiological features of breast cancer cell lines MDA-MB-231 and MCF-7. Cells were subject to an acid\u2013neutral\u2013base pH from 3.0 to 9.2, after which their membrane potential (Vm), cytoplasm conductivity \u03c3cyto, effective membrane conductance Geff, and \u03b6-potential were measured. Cells were also analyzed after permeabilization, to examine whether observed changes were due to cell surface chemistry, or to Vm. Both cell lines exhibited different electrophysiological phenotypes in acidic environments (pH &lt; 6.7); MDA-MB-231 exhibited statistically significant differences in \u03b6-potential, Vm, Geff and \u03c3cyto; MCF-7 only exhibited significant differences in \u03c3cyto. These findings suggest cells adapt to acidic microenvironments by altering Vm and potentially \u03b6-potential, reducing the extracellular potential, and hence potentially lowering proton concentration at the extracellular membrane surface. This offers new insights into potential therapeutic avenues to target the pH-dependent adaptations of cancer cells.<\/jats:p>","DOI":"10.3390\/mi17080902","type":"journal-article","created":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T08:52:01Z","timestamp":1785228721000},"page":"902","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Changes in Breast Cancer Cell Electrophysiology in Response to Culture Across a Wide Range of pH: Dielectrophoresis and \u03b6-Potential"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7382-2169","authenticated-orcid":false,"given":"Mary Krystelle","family":"Catacutan","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering and Biotechnology, Khalifa University of Science and Technology, Abu Dhabi 127788, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1699-8376","authenticated-orcid":false,"given":"Sungmun","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering and Biotechnology, Khalifa University of Science and Technology, Abu Dhabi 127788, United Arab Emirates"},{"name":"Healthcare Engineering Innovation Group, Department of Biomedical Engineering and Biotechnology, Khalifa University of Science and Technology, Abu Dhabi 127788, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7385-5876","authenticated-orcid":false,"given":"Michael Pycraft","family":"Hughes","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering and Biotechnology, Khalifa University of Science and Technology, Abu Dhabi 127788, United Arab Emirates"},{"name":"Biotechnology Center, Department of Biomedical Engineering and Biotechnology, Khalifa University of Science and Technology, Abu Dhabi 127788, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Hosonuma, M., and Yoshimura, K. (2023). Association between pH regulation of the tumor microenvironment and immunological state. Front. Oncol., 13.","DOI":"10.3389\/fonc.2023.1175563"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Bogdanov, A., Bogdanov, A., Chubenko, V., Volkov, N., Moiseenko, F., and Moiseyenko, V. (2022). Tumor acidity: From hallmark of cancer to target of treatment. Front. Oncol., 12.","DOI":"10.3389\/fonc.2022.979154"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Yang, M., and Brackenbury, W.J. (2013). Membrane potential and cancer progression. Front. Physiol., 4.","DOI":"10.3389\/fphys.2013.00185"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1126\/science.123.3191.309","article-title":"On the Origin of Cancer Cells","volume":"123","author":"Warburg","year":"1956","journal-title":"Science"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1186\/s13046-020-01709-5","article-title":"The role of microenvironment in tumor angiogenesis","volume":"39","author":"Jiang","year":"2020","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"3786","DOI":"10.1172\/JCI60534","article-title":"Heterogeneity in breast cancer","volume":"121","author":"Polyak","year":"2011","journal-title":"J. Clin. Investig."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Welsh, J. (2013). Animal Models for Studying Prevention and Treatment of Breast Cancer. Animal Models for the Study of Human Disease, Elsevier.","DOI":"10.1016\/B978-0-12-415894-8.00040-3"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Lin, J., Chen, L., and Lin, J. (2021). Thriving at Low pH: Adaptation Mechanisms of Acidophiles. Acidophiles\u2014Fundamentals and Applications, IntechOpen.","DOI":"10.5772\/intechopen.96620"},{"key":"ref_9","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":"Redmann","year":"1974","journal-title":"Exp. Cell Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1626","DOI":"10.1021\/bi00627a016","article-title":"Significance of surface potential in interaction of 8-anilino-1-naphthalenesulfonate with mitochondria: Fluorescence intensity and \u03b6 potential","volume":"16","author":"Aiuchi","year":"1977","journal-title":"Biochemistry"},{"key":"ref_11","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":"Hato","year":"1976","journal-title":"Biochim. Biophys. Acta (BBA)-Biomembr."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/0927-7757(93)80005-Y","article-title":"Biospecific mechanism of double layer formation and peculiarities of cell electrophoresis","volume":"73","author":"Dukhin","year":"1993","journal-title":"Colloids Surf. A Physicochem. Eng. Asp."},{"key":"ref_13","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":"Hughes","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_14","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":"Chacar","year":"2024","journal-title":"Meas. Sci. Technol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1089\/bioe.2021.0044","article-title":"The Platelet Electrome: Evidence for a Role in Regulation of Function and Surface Interaction","volume":"4","author":"Hughes","year":"2022","journal-title":"Bioelectricity"},{"key":"ref_16","unstructured":"Lyklema, H. (2005). Soft colloids. Fundamentals of Interface and Colloid Science, Elsevier Academic Press."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1038\/260799a0","article-title":"Single-channel currents recorded from membrane of denervated frog muscle fibres","volume":"260","author":"Neher","year":"1976","journal-title":"Nature"},{"key":"ref_18","first-page":"1","article-title":"Patch clamp technique: Review of the current state of the art and potential contributions from nanoengineering","volume":"222","author":"Zhao","year":"2009","journal-title":"Proc. Inst. Mech. Eng. Part N. J. Nanoeng. Nanosyst."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Pethig, R. (2017). Dielectrophoresis: Theory, Methodology, and Biological Applications, John Wiley & Sons, Inc.","DOI":"10.1002\/9781118671443"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2267","DOI":"10.1088\/0031-9155\/50\/10\/006","article-title":"Extraction of dielectric properties of multiple populations from dielectrophoretic collection spectrum data","volume":"50","author":"Broche","year":"2005","journal-title":"Phys. Med. Biol."},{"key":"ref_21","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":"Hughes","year":"2024","journal-title":"Sci. Rep."},{"key":"ref_22","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":"Hoettges","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_23","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":"Hughes","year":"2023","journal-title":"Electrophoresis"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.partic.2014.05.002","article-title":"Light scattering: A review of particle characterization applications","volume":"18","author":"Xu","year":"2015","journal-title":"Particuology"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1016\/j.ccr.2006.10.008","article-title":"A collection of breast cancer cell lines for the study of functionally distinct cancer subtypes","volume":"10","author":"Neve","year":"2006","journal-title":"Cancer Cell"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1010428319869101","DOI":"10.1177\/1010428319869101","article-title":"Characterization of the stemness potency of mammospheres isolated from the breast cancer cell lines","volume":"41","author":"Yousefnia","year":"2019","journal-title":"Tumour Biol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1186\/s13287-025-04850-0","article-title":"Electrophysiological analysis of human mesenchymal stem cells after cryopreservation yields markers of cell health","volume":"17","author":"Johnson","year":"2026","journal-title":"Stem Cell Res. Ther."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"22475","DOI":"10.1038\/s41598-025-06371-5","article-title":"Vm and \u03b6-potential of Candida albicans corelate with biofilm formation","volume":"15","author":"Johnson","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"15865","DOI":"10.1038\/s41598-025-98958-1","article-title":"Tracking chondrocyte-to-fibroblast transformation via changes in cell electrophysiology","volume":"15","author":"Clarke","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Kosmulski, M. (2009). Surface Charging and Points of Zero Charge, CRC Press.","DOI":"10.1201\/9781420051896"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"14342","DOI":"10.1021\/acs.est.1c01983","article-title":"Expanding Perspectives of Element Cycling from 1970 to 2020: The Influence of Stumm and Morgan","volume":"55","author":"Dzombak","year":"2021","journal-title":"Environ. Sci. Technol."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Jentoft, F.C. (2013). Solid Acids and Bases. Comprehensive Inorganic Chemistry II, Elsevier.","DOI":"10.1016\/B978-0-08-097774-4.00720-8"},{"key":"ref_33","unstructured":"Hunter, R.J., Ottewill, R.H., and Rowell, R.L. (2013). Zeta Potential in Colloid Science: Principles and Applications, Elsevier Science."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1081\/DIS-200054583","article-title":"The Determination of the Isoelectric Point from Measurements of Dispersion Viscosity as a Function of pH","volume":"26","author":"Liang","year":"2005","journal-title":"J. Dispers. Sci. Technol."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Gautschi, I., van Bemmelen, M.X., and Schild, L. (2017). Proton and non-proton activation of ASIC channels. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0175293"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"6408","DOI":"10.1039\/C6AN01596D","article-title":"Accurate quantification of apoptosis progression and toxicity using a dielectrophoretic approach","volume":"141","author":"Henslee","year":"2016","journal-title":"Analyst"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2063","DOI":"10.1021\/ac702083g","article-title":"Dielectrophoresis-activated multiwell Plate for label-free high-throughput Drug Assessment","volume":"80","author":"Hoettges","year":"2008","journal-title":"Anal. Chem."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1152\/physrev.00044.2016","article-title":"Ion Channels in Cancer: Are Cancer Hallmarks Oncochannelopathies?","volume":"98","author":"Prevarskaya","year":"2018","journal-title":"Physiol. Rev."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1499","DOI":"10.1021\/ed078p1499","article-title":"The Henderson-Hasselbalch Equation: Its History and Limitations","volume":"78","author":"Po","year":"2001","journal-title":"J. Chem. Educ."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1493","DOI":"10.1002\/elps.201500022","article-title":"Effects of cell detachment methods on the dielectric properties of adherent and suspension cells","volume":"36","author":"Mahabadi","year":"2015","journal-title":"Electrophoresis"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"672","DOI":"10.1186\/s40064-015-1476-7","article-title":"Alteration of Zeta potential and membrane permeability in bacteria: A study with cationic agents","volume":"4","author":"Halder","year":"2015","journal-title":"SpringerPlus"},{"key":"ref_42","first-page":"3728096","article-title":"Acid-Sensing Ion Channels as Potential Therapeutic Targets in Neurodegeneration and Neuroinflammation","volume":"2017","author":"Vega","year":"2017","journal-title":"Mediat. Inflamm."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Evlanenkov, K.K., Nikolaev, M.V., Potapieva, N.N., Bolshakov, K.V., and Tikhonov, D.B. (2023). Probing the Proton-Gated ASIC Channels Using Tetraalkylammonium Ions. Biomolecules, 13.","DOI":"10.3390\/biom13111631"}],"container-title":["Micromachines"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-666X\/17\/8\/902\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T08:55:25Z","timestamp":1785228925000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-666X\/17\/8\/902"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,28]]},"references-count":43,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["mi17080902"],"URL":"https:\/\/doi.org\/10.3390\/mi17080902","relation":{},"ISSN":["2072-666X"],"issn-type":[{"value":"2072-666X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,28]]}}}