{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T19:08:12Z","timestamp":1774033692586,"version":"3.50.1"},"reference-count":33,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2016,5,26]],"date-time":"2016-05-26T00:00:00Z","timestamp":1464220800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2016,5,26]],"date-time":"2016-05-26T00:00:00Z","timestamp":1464220800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>In this report, we showed that two tumor cell characteristics, namely the malignancy and drug-resistance status can be evaluated by their membrane resealing response. Specifically, membrane pores in a number of pairs of cancer and normal cell lines originated from nasopharynx, lung and intestine were introduced by nano-mechanical puncturing. Interestingly, such nanometer-sized holes in tumor cells can reseal ~2\u20133 times faster than those in the corresponding normal cells. Furthermore, the membrane resealing time in cancer cell lines exhibiting resistance to several leading chemotherapeutic drugs was also found to be substantially shorter than that in their drug-sensitive counterparts, demonstrating the potential of using this quantity as a novel marker for future cancer diagnosis and drug resistance detection. Finally, a simple model was proposed to explain the observed resealing dynamics of cells which suggested that the distinct response exhibited by normal, tumor and drug resistant cells is likely due to the different tension levels in their lipid membranes, a conclusion that is also supported by direct cortical tension measurement.<\/jats:p>","DOI":"10.1038\/srep26692","type":"journal-article","created":{"date-parts":[[2016,5,26]],"date-time":"2016-05-26T09:23:52Z","timestamp":1464254632000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Characterizing the malignancy and drug resistance of cancer cells from their membrane resealing response"],"prefix":"10.1038","volume":"6","author":[{"given":"T. H.","family":"Hui","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Z. L.","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H. W.","family":"Fong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roger K. C.","family":"Ngan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T. Y.","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joseph S. K.","family":"Au","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A. H. W.","family":"Ngan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Timothy T. C.","family":"Yip","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Y.","family":"Lin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2016,5,26]]},"reference":[{"key":"BFsrep26692_CR1","doi-asserted-by":"crossref","unstructured":"Pantel, K. & Alix-Panabi\u00e8res, C. Real-time Liquid Biopsy in Cancer Patients: Fact or Fiction? Cancer Research, 10.1158\/0008-5472.can-13-2030 (2013).","DOI":"10.1158\/0008-5472.CAN-13-2030"},{"key":"BFsrep26692_CR2","doi-asserted-by":"crossref","unstructured":"Mutter, G. L. et al. Involution and Progression to Carcinoma of Mutant Clones in Normal Endometrial Tissues. Cancer Research, 10.1158\/0008-5472.can-14-0108 (2014).","DOI":"10.1158\/0008-5472.CAN-14-0108"},{"key":"BFsrep26692_CR3","doi-asserted-by":"crossref","unstructured":"Tomaszewski, J. E. & LiVolsi, V. A. Mandatory second opinion of pathologic slides. Cancer 86, 2198\u20132200, 10.1002\/(SICI)1097-0142(19991201)86:11&lt;2198::AID-CNCR4&gt;3.0.CO;2-G (1999).","DOI":"10.1002\/(SICI)1097-0142(19991201)86:11<2198::AID-CNCR4>3.0.CO;2-G"},{"key":"BFsrep26692_CR4","doi-asserted-by":"publisher","first-page":"8643","DOI":"10.1158\/0008-5472.can-07-6611","volume":"68","author":"VT DeVita","year":"2008","unstructured":"DeVita, V. T. & Chu, E. A History of Cancer Chemotherapy. Cancer Research 68, 8643\u20138653, 10.1158\/0008-5472.can-07-6611 (2008).","journal-title":"Cancer Research"},{"key":"BFsrep26692_CR5","doi-asserted-by":"publisher","first-page":"675","DOI":"10.1002\/emmm.201101131","volume":"4","author":"NA Saunders","year":"2012","unstructured":"Saunders, N. A. et al. Role of intratumoural heterogeneity in cancer drug resistance: molecular and clinical perspectives. EMBO Mol Med 4, 675\u2013684, 10.1002\/emmm.201101131 (2012).","journal-title":"EMBO Mol Med"},{"key":"BFsrep26692_CR6","doi-asserted-by":"publisher","first-page":"4164","DOI":"10.1021\/nl301726g","volume":"12","author":"M Maltez-da Costa","year":"2012","unstructured":"Maltez-da Costa, M. et al. Simple Monitoring of Cancer Cells Using Nanoparticles. Nano Letters 12, 4164\u20134171, 10.1021\/nl301726g (2012).","journal-title":"Nano Letters"},{"key":"BFsrep26692_CR7","doi-asserted-by":"publisher","first-page":"312","DOI":"10.1016\/j.jmps.2013.08.018","volume":"62","author":"H Gao","year":"2014","unstructured":"Gao, H. Probing mechanical principles of cell\u2013nanomaterial interactions. Journal of the Mechanics and Physics of Solids 62, 312\u2013339, 10.1016\/j.jmps.2013.08.018 (2014).","journal-title":"Journal of the Mechanics and Physics of Solids"},{"key":"BFsrep26692_CR8","doi-asserted-by":"publisher","first-page":"636","DOI":"10.1021\/nl802990w","volume":"9","author":"GF Schneider","year":"2009","unstructured":"Schneider, G. F., Subr, V., Ulbrich, K. & Decher, G. Multifunctional Cytotoxic Stealth Nanoparticles. A Model Approach with Potential for Cancer Therapy. Nano Letters 9, 636\u2013642, 10.1021\/nl802990w (2009).","journal-title":"Nano Letters"},{"key":"BFsrep26692_CR9","doi-asserted-by":"publisher","first-page":"897","DOI":"10.1021\/bc049951i","volume":"15","author":"CM Goodman","year":"2004","unstructured":"Goodman, C. M., McCusker, C. D., Yilmaz, T. & Rotello, V. M. Toxicity of gold nanoparticles functionalized with cationic and anionic side chains. Bioconjug Chem 15, 897\u2013900, 10.1021\/bc049951i (2004).","journal-title":"Bioconjug Chem"},{"key":"BFsrep26692_CR10","doi-asserted-by":"publisher","first-page":"5881","DOI":"10.1016\/j.actamat.2003.09.001","volume":"51","author":"KJ Van Vliet","year":"2003","unstructured":"Van Vliet, K. J., Bao, G. & Suresh, S. The biomechanics toolbox: experimental approaches for living cells and biomolecules. Acta Materialia 51, 5881\u20135905, 10.1016\/j.actamat.2003.09.001 (2003).","journal-title":"Acta Materialia"},{"key":"BFsrep26692_CR11","doi-asserted-by":"publisher","first-page":"2994","DOI":"10.1529\/biophysj.105.067496","volume":"90","author":"MJ Rosenbluth","year":"2006","unstructured":"Rosenbluth, M. J., Lam, W. A. & Fletcher, D. A. Force microscopy of nonadherent cells: a comparison of leukemia cell deformability. Biophys J 90, 2994\u20133003, 10.1529\/biophysj.105.067496 (2006).","journal-title":"Biophys J"},{"key":"BFsrep26692_CR12","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1016\/j.colsurfb.2015.03.018","volume":"129","author":"S Jeon","year":"2015","unstructured":"Jeon, S., Yoo, C. Y. & Park, S. N. Improved stability and skin permeability of sodium hyaluronate-chitosan multilayered liposomes by Layer-by-Layer electrostatic deposition for quercetin delivery. Colloids Surf B Biointerfaces 129, 7\u201314, 10.1016\/j.colsurfb.2015.03.018 (2015).","journal-title":"Colloids Surf B Biointerfaces"},{"key":"BFsrep26692_CR13","doi-asserted-by":"publisher","first-page":"371","DOI":"10.1002\/wsbm.1275","volume":"6","author":"E Moeendarbary","year":"2014","unstructured":"Moeendarbary, E. & Harris, A. R. Cell mechanics: principles, practices and prospects. Wiley Interdisciplinary Reviews: Systems Biology and Medicine 6, 371\u2013388, 10.1002\/wsbm.1275 (2014).","journal-title":"Wiley Interdisciplinary Reviews: Systems Biology and Medicine"},{"key":"BFsrep26692_CR14","doi-asserted-by":"publisher","first-page":"3989","DOI":"10.1016\/j.actamat.2007.04.022","volume":"55","author":"S Suresh","year":"2007","unstructured":"Suresh, S. Biomechanics and biophysics of cancer cells. Acta Materialia 55, 3989\u20134014, 10.1016\/j.actamat.2007.04.022 (2007).","journal-title":"Acta Materialia"},{"key":"BFsrep26692_CR15","doi-asserted-by":"publisher","first-page":"5247","DOI":"10.1021\/nl402719q","volume":"13","author":"YT Wang","year":"2013","unstructured":"Wang, Y. T. et al. Nanomechanics insights into the performance of healthy and osteoporotic bones. Nano letters 13, 5247\u20135254, 10.1021\/nl402719q (2013).","journal-title":"Nano letters"},{"key":"BFsrep26692_CR16","doi-asserted-by":"publisher","first-page":"7074","DOI":"10.1038\/srep07074","volume":"4","author":"Y Fang","year":"2014","unstructured":"Fang, Y. et al. Investigating dynamic structural and mechanical changes of neuroblastoma cells associated with glutamate-mediated neurodegeneration. Scientific Reports 4, 7074, 10.1038\/srep07074 (2014).","journal-title":"Scientific Reports"},{"key":"BFsrep26692_CR17","doi-asserted-by":"publisher","first-page":"780","DOI":"10.1038\/nnano.2007.388","volume":"2","author":"SE Cross","year":"2007","unstructured":"Cross, S. E., Jin, Y. S., Rao, J. & Gimzewski, J. K. Nanomechanical analysis of cells from cancer patients. Nature Nanotechnology 2, 780\u2013783, 10.1038\/nnano.2007.388 (2007).","journal-title":"Nature Nanotechnology"},{"key":"BFsrep26692_CR18","doi-asserted-by":"publisher","first-page":"384003","DOI":"10.1088\/0957-4484\/19\/38\/384003","volume":"19","author":"SE Cross","year":"2008","unstructured":"Cross, S. E. et al. AFM-based analysis of human metastatic cancer cells. Nanotechnology 19, 384003, 10.1088\/0957-4484\/19\/38\/384003 (2008).","journal-title":"Nanotechnology"},{"key":"BFsrep26692_CR19","doi-asserted-by":"publisher","first-page":"5075","DOI":"10.1158\/0008-5472.can-11-0247","volume":"71","author":"V Swaminathan","year":"2011","unstructured":"Swaminathan, V. et al. Mechanical Stiffness Grades Metastatic Potential in Patient Tumor Cells and in Cancer Cell Lines. Cancer Research 71, 5075\u20135080, 10.1158\/0008-5472.can-11-0247 (2011).","journal-title":"Cancer Research"},{"key":"BFsrep26692_CR20","doi-asserted-by":"publisher","first-page":"522","DOI":"10.1038\/nnano.2013.120","volume":"8","author":"G Longo","year":"2013","unstructured":"Longo, G. et al. Rapid detection of bacterial resistance to antibiotics using AFM cantilevers as nanomechanical sensors. Nat Nanotechnol 8, 522\u2013526, 10.1038\/nnano.2013.120 (2013).","journal-title":"Nat Nanotechnol"},{"key":"BFsrep26692_CR21","doi-asserted-by":"publisher","first-page":"3256","DOI":"10.1158\/0008-5472.can-08-4055","volume":"69","author":"ML Sos","year":"2009","unstructured":"Sos, M. L. et al. PTEN loss contributes to erlotinib resistance in EGFR-mutant lung cancer by activation of Akt and EGFR. Cancer Res 69, 3256\u20133261, 10.1158\/0008-5472.can-08-4055 (2009).","journal-title":"Cancer Res"},{"key":"BFsrep26692_CR22","doi-asserted-by":"publisher","first-page":"1141","DOI":"10.3892\/or_00000965","volume":"24","author":"K Furugaki","year":"2010","unstructured":"Furugaki, K. et al. Schedule-dependent antitumor activity of the combination with erlotinib and docetaxel in human non-small cell lung cancer cells with EGFR mutation, KRAS mutation or both wild-type EGFR and KRAS. Oncol Rep 24, 1141\u20131146 (2010).","journal-title":"Oncol Rep"},{"key":"BFsrep26692_CR23","doi-asserted-by":"publisher","first-page":"907","DOI":"10.1016\/j.bpj.2008.10.035","volume":"96","author":"JH Kroeger","year":"2009","unstructured":"Kroeger, J. H., Vernon, D. & Grant, M. Curvature-driven pore growth in charged membranes during charge-pulse and voltage-clamp experiments. Biophys J 96, 907\u2013916, 10.1016\/j.bpj.2008.10.035 (2009).","journal-title":"Biophys J"},{"key":"BFsrep26692_CR24","doi-asserted-by":"publisher","first-page":"1001","DOI":"10.1016\/s0006-3495(89)82898-x","volume":"55","author":"D Needham","year":"1989","unstructured":"Needham, D. & Hochmuth, R. M. Electro-mechanical permeabilization of lipid vesicles. Role of membrane tension and compressibility. Biophys J 55, 1001\u20131009, 10.1016\/s0006-3495(89)82898-x (1989).","journal-title":"Biophys J"},{"key":"BFsrep26692_CR25","doi-asserted-by":"publisher","first-page":"18581","DOI":"10.1073\/pnas.0903353106","volume":"106","author":"JY Tinevez","year":"2009","unstructured":"Tinevez, J. Y. et al. Role of cortical tension in bleb growth. Proceedings of the National Academy of Sciences of the United States of America 106, 18581\u201318586 (2009).","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"key":"BFsrep26692_CR26","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s11671-015-1174-y","volume":"10","author":"X Zhao","year":"2015","unstructured":"Zhao, X. et al. Discrimination Between Cervical Cancer Cells and Normal Cervical Cells Based on Longitudinal Elasticity Using Atomic Force Microscopy. Nanoscale Research Letters 10, 1\u20138, 10.1186\/s11671-015-1174-y (2015).","journal-title":"Nanoscale Research Letters"},{"key":"BFsrep26692_CR27","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1111\/j.1749-6632.1994.tb30438.x","volume":"720","author":"J Teissie","year":"1994","unstructured":"Teissie, J. & Rols, M. P. Manipulation of cell cytoskeleton affects the lifetime of cell membrane electropermeabilization. Annals of the New York Academy of Sciences 720, 98\u2013110 (1994).","journal-title":"Annals of the New York Academy of Sciences"},{"key":"BFsrep26692_CR28","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1016\/0005-2736(92)90272-N","volume":"1111","author":"MP Rols","year":"1992","unstructured":"Rols, M. P. & Teissie, J. Experimental evidence for the involvement of the cytoskeleton in mammalian cell electropermeabilization. Biochim Biophys Acta 1111, 45\u201350 (1992).","journal-title":"Biochim Biophys Acta"},{"key":"BFsrep26692_CR29","doi-asserted-by":"publisher","first-page":"2780","DOI":"10.1242\/jcs.03006","volume":"119","author":"T Togo","year":"2006","unstructured":"Togo, T. Disruption of the plasma membrane stimulates rearrangement of microtubules and lipid traffic toward the wound site. Journal of Cell Science 119, 2780\u20132786, 10.1242\/jcs.03006 (2006).","journal-title":"Journal of Cell Science"},{"key":"BFsrep26692_CR30","doi-asserted-by":"publisher","first-page":"475","DOI":"10.1007\/s10439-013-0923-2","volume":"42","author":"RE Neal","year":"2014","unstructured":"Neal, R. E. et al. In vitro and numerical support for combinatorial irreversible electroporation and electrochemotherapy glioma treatment. Ann Biomed Eng 42, 475\u2013487, 10.1007\/s10439-013-0923-2 (2014).","journal-title":"Ann Biomed Eng"},{"key":"BFsrep26692_CR31","doi-asserted-by":"publisher","first-page":"480","DOI":"10.1016\/j.tibtech.2015.06.002","volume":"33","author":"T Kotnik","year":"2015","unstructured":"Kotnik, T. et al. Electroporation-based applications in biotechnology. Trends Biotechnol 33, 480\u2013488, 10.1016\/j.tibtech.2015.06.002 (2015).","journal-title":"Trends Biotechnol"},{"key":"BFsrep26692_CR32","doi-asserted-by":"publisher","first-page":"467","DOI":"10.4155\/tde.14.10","volume":"5","author":"Z Fan","year":"2014","unstructured":"Fan, Z., Kumon, R. E. & Deng, C. X. Mechanisms of microbubble-facilitated sonoporation for drug and gene delivery. Ther Deliv 5, 467\u2013486, 10.4155\/tde.14.10 (2014).","journal-title":"Ther Deliv"},{"key":"BFsrep26692_CR33","doi-asserted-by":"publisher","first-page":"2393","DOI":"10.1016\/j.ultrasmedbio.2013.08.003","volume":"39","author":"Y Hu","year":"2013","unstructured":"Hu, Y., Wan, J. M. & Yu, A. C. Membrane perforation and recovery dynamics in microbubble-mediated sonoporation. Ultrasound Med Biol 39, 2393\u20132405, 10.1016\/j.ultrasmedbio.2013.08.003 (2013).","journal-title":"Ultrasound Med Biol"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/srep26692","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep26692.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep26692.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,4]],"date-time":"2023-01-04T14:43:05Z","timestamp":1672843385000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/srep26692"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,5,26]]},"references-count":33,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2016,7,18]]}},"alternative-id":["BFsrep26692"],"URL":"https:\/\/doi.org\/10.1038\/srep26692","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,5,26]]},"assertion":[{"value":"8 February 2016","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 May 2016","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 May 2016","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"26692"}}