{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T13:36:42Z","timestamp":1790948202003,"version":"4.1.0"},"reference-count":79,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"39","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2025,9,26]]},"abstract":"<jats:p>Pulmonary surfactants reduce the work of breathing, enhance compliance, and prevent alveolar collapse. Yet, their role extends beyond that of a simple surfactant; otherwise, exogenous surfactant therapy would fully restore compliance in acute respiratory distress syndrome (ARDS) by increasing surface concentration alone. Here, we show that interfacial microstructure and mechanics, regulated by spontaneous or ventilator-induced sighs, play a critical role. Using interfacial rheometry and structural analysis, including in situ neutron reflectometry and Raman-based techniques, we find that sighs enrich the air-liquid interface with saturated lipids, triggering structural rearrangements. This periodic \u201creset\u201d transforms the layer into a mechanically robust, DPPC-rich film, where compressional hardening counteracts tension. These findings highlight the nonequilibrium dynamics of surfactant layers and underscore the importance of interfacial compressive stresses, not just tension, in governing lung mechanics. This mechanism helps sustain low interfacial stress and high compliance, offering mechanistic insight to guide protective ventilation strategies upon lung trauma and possibilities to optimize surfactant-enabled pulmonary treatment.<\/jats:p>","DOI":"10.1126\/sciadv.adx6034","type":"journal-article","created":{"date-parts":[[2025,9,24]],"date-time":"2025-09-24T17:58:41Z","timestamp":1758736721000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":6,"title":["How sighing regulates pulmonary surfactant structure and its role in breathing mechanics"],"prefix":"10.1126","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-4759-7242","authenticated-orcid":true,"given":"Maria C.","family":"Novaes-Silva","sequence":"first","affiliation":[{"name":"Department of Materials, ETH Z\u00fcrich, Z\u00fcrich, 8093, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8239-2487","authenticated-orcid":true,"given":"Mariana","family":"Rodr\u00edguez-Hakim","sequence":"additional","affiliation":[{"name":"Department of Materials, ETH Z\u00fcrich, Z\u00fcrich, 8093, Switzerland."},{"name":"Departamento de F\u00edsica Fundamental, Universidad Nacional de Educaci\u00f3n a Distancia, Las Rozas de Madrid, E28232, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8309-9522","authenticated-orcid":true,"given":"Benjamin R.","family":"Thompson","sequence":"additional","affiliation":[{"name":"Chemical and Biomolecular Engineering Department, University of Delaware, Newark, DE 19716, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9565-619X","authenticated-orcid":true,"given":"Norman J.","family":"Wagner","sequence":"additional","affiliation":[{"name":"Chemical and Biomolecular Engineering Department, University of Delaware, Newark, DE 19716, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4725-3107","authenticated-orcid":true,"given":"Eline","family":"Hermans","sequence":"additional","affiliation":[{"name":"Department of Chemical Engineering, University of Leuven, Leuven, 3001, Belgium."},{"name":"Department of Pharmaceutical and Material Sciences, Johnson &amp; Johnson Innovative Medicine, Beerse, 2340, Belgium."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3961-1522","authenticated-orcid":true,"given":"Lieven J.","family":"Dupont","sequence":"additional","affiliation":[{"name":"Laboratory of Respiratory Diseases and Thoracic Surgery (BREATHE), KU Leuven, Leuven, 3000, Belgium."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0352-0656","authenticated-orcid":true,"given":"Jan","family":"Vermant","sequence":"additional","affiliation":[{"name":"Department of Materials, ETH Z\u00fcrich, Z\u00fcrich, 8093, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamem.2008.05.003"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF02621963"},{"key":"e_1_3_2_4_2","first-page":"341","article-title":"Mortality associated with acute respiratory distress syndrome, 2009-2019: A systematic review and meta-analysis","volume":"24","author":"Sadana D.","year":"2022","unstructured":"D. Sadana, S. Kaur, K. Sankaramangalam, I. Saini, K. Banerjee, M. Siuba, V. Amaral, S. Gadre, H. Torbic, S. Krishnan, A. Duggal, Mortality associated with acute respiratory distress syndrome, 2009-2019: A systematic review and meta-analysis. Crit. Care Resusc. 24, 341\u2013351 (2022).","journal-title":"Crit. Care Resusc."},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1136\/thoraxjnl-2020-215950"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12890-018-0761-y"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.4187\/respcare.01306"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.chemrev.3c00146"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2309900120"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1039\/D0SM00415D"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.abb.2021.108850"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI104012"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1959.14.5.669"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.3389\/fvets.2023.1157026"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13054-014-0474-4"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00134-009-1439-y"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2023.21739"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1097\/00003246-200108000-00014"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1715830115"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpj.2020.06.033"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00101.2023"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1529\/biophysj.104.051201"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-chembioeng-061010-114202"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cocis.2018.09.005"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00058.2024"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1039\/D1SM00337B"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1039\/C5SM01603G"},{"key":"e_1_3_2_28_2","doi-asserted-by":"crossref","unstructured":"D. Thomas J. Marriott R. Vadlamudi B. Efendie L. L. Maine \u201cChapter 1 - Introduction to clinical practice research and pharmacy education\u201d in Clinical Pharmacy Education Practice and Research (Elsevier 2019) pp. 1\u20139.","DOI":"10.1016\/B978-0-12-814276-9.00001-5"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cis.2017.07.008"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2016.09.006"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.1990.70.4.1117"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1986.60.4.1341"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1039\/C7SM01100H"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.langmuir.0c02234"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1513\/AnnalsATS.201411-507FR"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1038\/srep40889"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.analchem.1c04054"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/0005-2736(80)90512-X"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/0006-291X(73)90930-3"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1021\/jp0735886"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.saa.2017.06.060"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/0005-2736(77)90078-5"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1063\/5.0090350"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1021\/la1048985"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1021\/ma00077a052"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamem.2006.10.004"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1039\/C3SM52091A"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1529\/biophysj.107.113399"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamem.2016.02.030"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamem.2010.04.006"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpj.2011.02.019"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2020.02.028"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.3390\/sym13071259"},{"key":"e_1_3_2_54_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamem.2020.183216"},{"key":"e_1_3_2_55_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2020.166749"},{"key":"e_1_3_2_56_2","doi-asserted-by":"publisher","DOI":"10.1096\/fj.15-273458"},{"key":"e_1_3_2_57_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-3495(01)75865-1"},{"key":"e_1_3_2_58_2","doi-asserted-by":"publisher","DOI":"10.1529\/biophysj.107.111823"},{"key":"e_1_3_2_59_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-3495(03)74723-7"},{"key":"e_1_3_2_60_2","doi-asserted-by":"publisher","DOI":"10.1021\/la036150f"},{"key":"e_1_3_2_61_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0959-440X(02)00352-4"},{"key":"e_1_3_2_62_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-3495(01)76156-5"},{"key":"e_1_3_2_63_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chemphyslip.2014.09.002"},{"key":"e_1_3_2_64_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamem.2009.12.010"},{"key":"e_1_3_2_65_2","doi-asserted-by":"publisher","DOI":"10.3390\/diagnostics13182964"},{"key":"e_1_3_2_66_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcis.2014.10.067"},{"key":"e_1_3_2_67_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cis.2020.102295"},{"key":"e_1_3_2_68_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.langmuir.6b03258"},{"key":"e_1_3_2_69_2","doi-asserted-by":"publisher","DOI":"10.1021\/la101870m"},{"key":"e_1_3_2_70_2","doi-asserted-by":"crossref","unstructured":"M. C. Petty W. A. Barlow \u201cFilm deposition\u201d in Langmuir-Blodgett Films (Springer 1990) pp. 93\u2013123.","DOI":"10.1007\/978-1-4899-3716-2_3"},{"key":"e_1_3_2_71_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.85.2194.76.b"},{"key":"e_1_3_2_72_2","doi-asserted-by":"publisher","DOI":"10.1140\/epjp\/i2011-11107-8"},{"key":"e_1_3_2_73_2","doi-asserted-by":"publisher","DOI":"10.1107\/S160057671800448X"},{"key":"e_1_3_2_74_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cocis.2011.11.001"},{"key":"e_1_3_2_75_2","doi-asserted-by":"publisher","DOI":"10.1515\/IJNSNS.2009.10.3.273"},{"key":"e_1_3_2_76_2","doi-asserted-by":"publisher","DOI":"10.1021\/acsomega.7b01270"},{"key":"e_1_3_2_77_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamem.2004.11.001"},{"key":"e_1_3_2_78_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.physb.2004.03.227"},{"key":"e_1_3_2_79_2","doi-asserted-by":"publisher","DOI":"10.1051\/epjconf\/202023603002"},{"key":"e_1_3_2_80_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamem.2011.12.007"}],"container-title":["Science Advances"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/sciadv.adx6034","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,24]],"date-time":"2025-09-24T17:59:27Z","timestamp":1758736767000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/sciadv.adx6034"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,26]]},"references-count":79,"journal-issue":{"issue":"39","published-print":{"date-parts":[[2025,9,26]]}},"alternative-id":["10.1126\/sciadv.adx6034"],"URL":"https:\/\/doi.org\/10.1126\/sciadv.adx6034","relation":{},"ISSN":["2375-2548"],"issn-type":[{"value":"2375-2548","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,26]]},"assertion":[{"value":"2025-03-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-08-28","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-09-24","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"eadx6034"}}