{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T15:52:24Z","timestamp":1789487544251,"version":"build-2803163510"},"reference-count":40,"publisher":"American Chemical Society (ACS)","issue":"36","license":[{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico","doi-asserted-by":"publisher","award":["311933\/2021-1"],"award-info":[{"award-number":["311933\/2021-1"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico","doi-asserted-by":"publisher","award":["401604\/2022-5"],"award-info":[{"award-number":["401604\/2022-5"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico","doi-asserted-by":"publisher","award":["406761\/2022-1"],"award-info":[{"award-number":["406761\/2022-1"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The permeability of the skin barrier is not fixed\u2500it emerges from the molecular organization of its lipid matrix. In the stratum corneum, compositional alterations associated with dermatological conditions reshape this organization, yet how these changes influence electrically induced transport remains unclear. Here, we employ fully atomistic nonequilibrium molecular dynamics simulations to uncover how lipid composition is mechanically encoded into electroporation response in biomimetic SC lipid membranes. Eleven membrane models spanning ceramide-rich, cholesterol-rich, and physiologically balanced compositions were systematically investigated. We find that electroporation susceptibility is not dictated by individual lipid species but by the collective mechanical state encoded in membrane packing. Cholesterol-rich membranes exhibit rapid pore nucleation and form large conductive defects, whereas ceramide-dominated systems resist pore formation within the simulated time scale. Intermediate compositions display delayed nucleation and reduced pore sizes. The physiologically balanced SCbase membrane exhibits delayed pore formation and comparatively small conductive defects, consistent with a mechanically resilient yet not pore-immune regime. By linking pore nucleation events and time-resolved water transport to equilibrium structural descriptors, we show that bilayer thickness, interfacial cohesion, and lipid organization collectively define the effective barrier to defect formation. These results establish a predictive framework connecting compositional alterations\u2500relevant to both healthy and compromised skin\u2500to electrically induced permeability, providing molecular-level insights into barrier resilience and strategies for controlled transdermal transport.<\/jats:p>","DOI":"10.1021\/acsomega.6c04148","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T10:34:08Z","timestamp":1788431648000},"page":"54029-54040","source":"Crossref","is-referenced-by-count":0,"title":["From Lipid Composition\nto Electroporation: Mechanical\nEncoding of Barrier Resilience in Stratum Corneum Membranes"],"prefix":"10.1021","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0321-2290","authenticated-orcid":true,"given":"Neila Cristina Fonseca","family":"Machado","sequence":"first","affiliation":[{"name":"Universidade Federal do ABC, Centro de Cie\u0302ncias Naturais e Humanas , Av. dos Estados 5001 , , ,","place":["Santo Andre\u0301, Sa\u0303o Paulo, Brasil, 09210-580"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4392-0187","authenticated-orcid":true,"given":"Nicola\u0301s A.","family":"Garci\u0301a","sequence":"additional","affiliation":[{"name":"Universidad Nacional del Sur , Av.L.N.Alem, 1253 , , ,","place":["Bahi\u0301a Blanca, Buenos Aires, Argentina, B8000CPB"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nuria","family":"Anguita-Ortiz","sequence":"additional","affiliation":[{"name":"Universidad Auto\u0301noma de Madrid , , Calle Francisco Toma\u0301s y Valiente, 7 , ,","place":["Madrid, Spain, 28049"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorena","family":"Ruano","sequence":"additional","affiliation":[{"name":"Universidad Auto\u0301noma de Madrid , , Calle Francisco Toma\u0301s y Valiente, 7 , ,","place":["Madrid, Spain, 28049"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7419-5670","authenticated-orcid":true,"given":"Juan J.","family":"Nogueira","sequence":"additional","affiliation":[{"name":"Universidad Auto\u0301noma de Madrid , , Calle Francisco Toma\u0301s y Valiente, 7 , ,","place":["Madrid, Spain, 28049"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7690-014X","authenticated-orcid":true,"given":"Herculano da Silva","family":"Martinho","sequence":"additional","affiliation":[{"name":"Universidade Federal do ABC, Centro de Cie\u0302ncias Naturais e Humanas , Av. dos Estados 5001 , , ,","place":["Santo Andre\u0301, Sa\u0303o Paulo, Brasil, 09210-580"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,9,1]]},"reference":[{"key":"2026091510092553500_cit1","doi-asserted-by":"publisher","first-page":"S44","DOI":"10.1038\/jid.1983.12","article-title":"Epidermal\nlipids, barrier function, and desquamation","volume":"80","author":"Elias","year":"1983","journal-title":"J. Invest. Dermatol."},{"key":"2026091510092553500_cit2","doi-asserted-by":"publisher","first-page":"412","DOI":"10.1111\/ics.12049","article-title":"Filaggrin\u2013revisited","volume":"35","author":"Harding","year":"2013","journal-title":"Int.\nJ. Cosmet. Sci."},{"key":"2026091510092553500_cit3","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/S0163-7827(02)00028-0","article-title":"Structure\nof the skin barrier and its modulation by\nvesicular formulations","volume":"42","author":"Bouwstra","year":"2003","journal-title":"Prog. Lipid Res."},{"key":"2026091510092553500_cit4","first-page":"2420","article-title":"Skin lipids: localization\nand functional significance","volume":"1848","author":"Mojumdar","year":"2015","journal-title":"Biochim. Biophys.\nActa Biomembr."},{"key":"2026091510092553500_cit5","first-page":"505","article-title":"Structure and stability of ceramide\nbilayers: a molecular dynamics study","volume":"512","author":"Del Regno","year":"2018","journal-title":"J. Colloid\nInterface Sci."},{"key":"2026091510092553500_cit6","first-page":"426","article-title":"Ceramide structure and organization\nin skin barrier models","volume":"52","author":"Groen","year":"2011","journal-title":"J. Lipid Res."},{"key":"2026091510092553500_cit7","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/S0378-5173(98)00360-3","article-title":"Iontophoresis\nand electroporation:\ncomparisons and contrasts","volume":"179","author":"Banga","year":"1999","journal-title":"Int. J. Pharm."},{"key":"2026091510092553500_cit8","doi-asserted-by":"publisher","first-page":"106","DOI":"10.1159\/000091978","article-title":"Overcoming the stratum\ncorneum: the modulation of skin\npenetration: a review","volume":"19","author":"Trommer","year":"2006","journal-title":"Skin Pharmacol. Physiol."},{"key":"2026091510092553500_cit9","doi-asserted-by":"publisher","first-page":"12407","DOI":"10.1039\/C5CP00629E","article-title":"Perspectives on external electric fields in molecular\nsimulation: progress, prospects and challenges","volume":"17","author":"English","year":"2015","journal-title":"Phys. Chem. Chem. Phys."},{"key":"2026091510092553500_cit10","doi-asserted-by":"publisher","first-page":"8273","DOI":"10.1039\/D1CP00354B","article-title":"Tuning the transdermal\ntransport by application of external continuous electric field: A\ncoarse-grained molecular dynamics study","volume":"23","author":"Machado","year":"2021","journal-title":"Phys.\nChem. Chem. Phys."},{"key":"2026091510092553500_cit11","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1016\/S0169-409X(98)00065-9","article-title":"Effects of\niontophoresis and electroporation\non the stratum corneum: review of the biophysical studies","volume":"35","author":"Jadoul","year":"1999","journal-title":"Adv. Drug Delivery Rev."},{"key":"2026091510092553500_cit12","doi-asserted-by":"publisher","first-page":"657","DOI":"10.1016\/S0190-9622(96)80069-7","article-title":"Physical\nenhancement of dermatologic\ndrug delivery: iontophoresis and phonophoresis","volume":"34","author":"Kassan","year":"1996","journal-title":"J. Am. Acad. Dermatol."},{"key":"2026091510092553500_cit13","doi-asserted-by":"publisher","first-page":"6382","DOI":"10.1021\/ja029504i","article-title":"Simulation of pore\nformation in lipid bilayers by mechanical stress and electric fields","volume":"125","author":"Tieleman","year":"2003","journal-title":"J. Am. Chem. Soc."},{"key":"2026091510092553500_cit14","doi-asserted-by":"publisher","first-page":"2156","DOI":"10.1016\/S0006-3495(04)74275-7","article-title":"Molecular dynamics simulations of\nhydrophilic pores in lipid bilayers","volume":"86","author":"Leontiadou","year":"2004","journal-title":"Biophys.\nJ."},{"key":"2026091510092553500_cit15","first-page":"4924","article-title":"Mechanism of electroporation\nin lipid bilayers","volume":"10","author":"Bennett","year":"2014","journal-title":"J. Chem. Theory Comput."},{"key":"2026091510092553500_cit16","doi-asserted-by":"publisher","first-page":"2266","DOI":"10.1016\/j.bbamem.2015.12.031","article-title":"Membrane\npore formation in atomistic and coarse-grained\nsimulations","volume":"1858","author":"Kirsch","year":"2016","journal-title":"Biochim. Biophys. Acta Biomembr."},{"key":"2026091510092553500_cit17","first-page":"231","article-title":"Electroporation: From\nmolecular dynamics to clinical applications","volume":"51","author":"Rems","year":"2022","journal-title":"Annu. Rev. Biophys."},{"key":"2026091510092553500_cit18","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1146\/annurev-biophys-052118-115451","article-title":"Membrane Electroporation\nand Electropermeabilization: Mechanisms and Models","volume":"48","author":"Kotnik","year":"2019","journal-title":"Annu. Rev. Biophys."},{"key":"2026091510092553500_cit19","doi-asserted-by":"publisher","first-page":"523","DOI":"10.1111\/1523-1747.ep12470233","article-title":"Decreased level of\nceramides in stratum corneum of\natopic dermatitis: an etiologic factor in atopic dry skin?","volume":"96","author":"Imokawa","year":"1991","journal-title":"J. Invest. Dermatol."},{"key":"2026091510092553500_cit20","doi-asserted-by":"publisher","first-page":"2755","DOI":"10.1194\/jlr.p030338","article-title":"Increase in short-chain\nceramides correlates with an altered lipid\norganization and decreased barrier function in atopic eczema patients","volume":"53","author":"Janssens","year":"2012","journal-title":"J. Lipid Res."},{"key":"2026091510092553500_cit21","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1080\/00015559850135788","article-title":"Ceramide and\ncholesterol composition of the skin of patients with atopic dermatitis","volume":"78","author":"Di","year":"1998","journal-title":"Acta Derm.-Venereol."},{"key":"2026091510092553500_cit22","doi-asserted-by":"publisher","first-page":"2511","DOI":"10.1038\/jid.2010.161","article-title":"Changes\nin the ceramide profile of atopic dermatitis\npatients","volume":"130","author":"Ishikawa","year":"2010","journal-title":"J. Invest. Dermatol."},{"key":"2026091510092553500_cit23","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1186\/s12895-020-00102-1","article-title":"The ceramide\n[NP]\/[NS] ratio in the stratum corneum\nis a potential marker for skin properties and epidermal differentiation","volume":"20","author":"Yokose","year":"2020","journal-title":"BMC Dermatol."},{"key":"2026091510092553500_cit24","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1016\/0005-2736(88)90202-7","article-title":"Theoretical description of transient\npores in lipid\nbilayers","volume":"940","author":"Glaser","year":"1988","journal-title":"Biochim. Biophys. Acta Biomembr."},{"key":"2026091510092553500_cit25","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1016\/S0302-4598(96)05062-3","article-title":"Theory\nof electroporation: a review","volume":"41","author":"Weaver","year":"1996","journal-title":"Bioelectrochem.\nBioenerg."},{"key":"2026091510092553500_cit26","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1016\/S0304-4157(00)00016-2","article-title":"Structure\nof lipid bilayers","volume":"1469","author":"Nagle","year":"2000","journal-title":"Biochim. Biophys. Acta Rev.\nBiomembr."},{"key":"2026091510092553500_cit27","doi-asserted-by":"publisher","first-page":"7830","DOI":"10.1021\/jp101759q","article-title":"Update\nof the CHARMM all-atom additive\nforce field for lipids","volume":"114","author":"Klauda","year":"2010","journal-title":"J. Phys. Chem. B"},{"key":"2026091510092553500_cit28","first-page":"183954","article-title":"Lipid organization and membrane mechanics: recent advances\nfrom simulations","volume":"1864","author":"Wang","year":"2022","journal-title":"Biochim. Biophys. Acta Gen.\nSubj."},{"key":"2026091510092553500_cit29","unstructured":"Case, D. A.; et al.; AMBER\n22 Reference Manual; University of California, 2022."},{"key":"2026091510092553500_cit30","doi-asserted-by":"publisher","first-page":"1726","DOI":"10.1021\/acs.jctc.1c01217","article-title":"Lipid21: Complex Lipid Membrane Simulations\nwith AMBER","volume":"18","author":"Dickson","year":"2022","journal-title":"J. Chem. Theory Comput."},{"key":"2026091510092553500_cit31","doi-asserted-by":"publisher","first-page":"1859","DOI":"10.1002\/jcc.20945","article-title":"CHARMM-GUI: a web-based\ngraphical\nuser interface for CHARMM","volume":"29","author":"Jo","year":"2008","journal-title":"J. Comput. Chem."},{"key":"2026091510092553500_cit32","doi-asserted-by":"publisher","first-page":"926","DOI":"10.1063\/1.445869","article-title":"Comparison\nof simple potential functions for simulating liquid water","volume":"79","author":"Jorgensen","year":"1983","journal-title":"J. Chem. Phys."},{"key":"2026091510092553500_cit33","doi-asserted-by":"publisher","first-page":"952","DOI":"10.1002\/jcc.540130805","article-title":"Settle: An analytical\nversion of the SHAKE and RATTLE\nalgorithm for rigid water models","volume":"13","author":"Miyamoto","year":"1992","journal-title":"J. Comput.\nChem."},{"key":"2026091510092553500_cit34","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1023\/A:1007907925007","article-title":"Adventures\nin improving the scaling and accuracy of a parallel molecular dynamics\nprogram","volume":"11","author":"Crowley","year":"1997","journal-title":"J. Supercomput."},{"key":"2026091510092553500_cit35","doi-asserted-by":"publisher","first-page":"1759","DOI":"10.1016\/S0022-2275(20)31502-9","article-title":"Phase behavior of lipid\nmixtures based on human ceramides: coexistence of crystalline and\nliquid phases","volume":"42","author":"Bouwstra","year":"2001","journal-title":"J. Lipid Res."},{"key":"2026091510092553500_cit36","first-page":"5700","article-title":"Skin hydration:\ninterplay\nbetween molecular structure, lamellar organization, and water dynamics","volume":"11","author":"Mojumdar","year":"2015","journal-title":"Soft Matter"},{"key":"2026091510092553500_cit37","first-page":"6472","article-title":"Mechanistic insight into lipid organization\nin the stratum corneum using coarse-grained molecular dynamics simulations","volume":"14","author":"Del Regno","year":"2018","journal-title":"Soft Matter"},{"key":"2026091510092553500_cit38","first-page":"245101","article-title":"Water defect and pore formation in atomistic and coarse-grained\nlipid membranes","volume":"140","author":"Bennett","year":"2014","journal-title":"J. Chem. Phys."},{"key":"2026091510092553500_cit39","first-page":"1425","article-title":"Life cycle of an electropore: Field-dependent and field-independent\nsteps in pore creation and annihilation","volume":"102","author":"Levine","year":"2012","journal-title":"Biophys.\nJ."},{"key":"2026091510092553500_cit40","first-page":"1172","article-title":"Cholesterol modulates\nmembrane defects and water penetration in lipid bilayers","volume":"132","author":"Sengupta","year":"2010","journal-title":"J. Am. Chem. Soc."}],"container-title":["ACS Omega"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acsomega.6c04148","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/acsodf\/article-pdf\/11\/36\/54029\/68105631\/acsomega.6c04148.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/acsodf\/article-pdf\/11\/36\/54029\/68105631\/acsomega.6c04148.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T14:50:02Z","timestamp":1789483802000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/acsodf\/article\/11\/36\/54029\/5396184\/From-Lipid-Composition-to-Electroporation"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,1]]},"references-count":40,"journal-issue":{"issue":"36","published-online":{"date-parts":[[2026,9,1]]},"published-print":{"date-parts":[[2026,9,15]]}},"URL":"https:\/\/doi.org\/10.1021\/acsomega.6c04148","relation":{},"ISSN":["2470-1343"],"issn-type":[{"value":"2470-1343","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,1]]}}}