{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T22:06:06Z","timestamp":1790201166221,"version":"4.1.0"},"reference-count":78,"publisher":"American Chemical Society (ACS)","issue":"32","license":[{"start":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T00:00:00Z","timestamp":1785801600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T00:00:00Z","timestamp":1785801600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T00:00:00Z","timestamp":1785801600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-045"}],"funder":[{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["1R21GM153048-01"],"award-info":[{"award-number":["1R21GM153048-01"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health (NIH)","doi-asserted-by":"crossref","award":["S10 OD032268"],"award-info":[{"award-number":["S10 OD032268"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,8,19]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Membrane tension, defined as the in-plane mechanical stress of the lipid bilayer, encodes membrane stretch and lipid packing density. Despite its central role in regulating cellular behavior, measuring membrane tension in a direct and noninvasive way in deeper tissue (beyond microscopy) remains a major challenge. Here, we report a supramolecular strategy that transduces membrane mechanics into a spectrally resolved photoacoustic signal through lipid bilayer-confined J-aggregation. We employ two complementary probes: a fluorescence-active system to report aggregation behavior in the lipid bilayer of LUVs and an optimized analogue to enable cellular photoacoustic readout. We found that amphipathic BODIPY-based probes are inserted into lipid membranes and exist as either monomers or slip-stacked J-aggregates with aggregate populations dictated by lipid packing density, which is in turn influenced by membrane tension or lipid composition. Only ordered J-aggregates formed under membrane-confined conditions enable efficient conversion of absorbed light into PA805 signals. Kinetically driven large aggregates spectrally observable via absorption experiments in protein-rich environments are inactive in photoacoustic mode. This decoupling between optical absorption and photoacoustic output reveals aggregate geometry as a critical determinant of photothermal efficiency. Furthermore, the bilayer-confined PA805 on\/off behavior minimizes background signals from uninserted probes, enabling wash-free photoacoustic imaging. In model membranes and live cells, PA805 inversely correlates with lipid packing density, enabling noninvasive readout of membrane tension-associated changes.<\/jats:p>","DOI":"10.1021\/jacs.6c07895","type":"journal-article","created":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T19:02:08Z","timestamp":1785870128000},"page":"34339-34351","source":"Crossref","is-referenced-by-count":1,"title":["Lipid Bilayer-Confined\nJ-Aggregation Transduces\nCell Membrane Mechanics into Photoacoustic Signals"],"prefix":"10.1021","volume":"148","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-9539-4598","authenticated-orcid":true,"given":"Yong","family":"Hua","sequence":"first","affiliation":[{"name":"University of California San Diego , , La Jolla, , ,","place":["San Diego, California, United States, 92093"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-9113-8510","authenticated-orcid":true,"given":"Moumita","family":"Halder","sequence":"additional","affiliation":[{"name":"University of California San Diego , , La Jolla, , ,","place":["San Diego, California, United States, 92093"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5715-5060","authenticated-orcid":true,"given":"Lubna","family":"Amer","sequence":"additional","affiliation":[{"name":"University of California San Diego , , La Jolla, , ,","place":["San Diego, California, United States, 92093"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2328-8740","authenticated-orcid":true,"given":"Suhel","family":"Khan","sequence":"additional","affiliation":[{"name":"University of California San Diego , , La Jolla, , ,","place":["San Diego, California, United States, 92093"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei-Ze","family":"Wang","sequence":"additional","affiliation":[{"name":"University of California San Diego , , La Jolla, , ,","place":["San Diego, California, United States, 92093"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-3616-1583","authenticated-orcid":true,"given":"Benjamin","family":"Lam","sequence":"additional","affiliation":[{"name":"University of California San Diego , , La Jolla, , ,","place":["San Diego, California, United States, 92093"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9509-1336","authenticated-orcid":true,"given":"Mohammad","family":"Souri","sequence":"additional","affiliation":[{"name":"University of California San Diego , , La Jolla, , ,","place":["San Diego, California, United States, 92093"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2829-6408","authenticated-orcid":true,"given":"Jesse V.","family":"Jokerst","sequence":"additional","affiliation":[{"name":"University of California San Diego , , La Jolla, , ,","place":["San Diego, California, United States, 92093"]},{"name":"University of California San Diego , , La Jolla, , ,","place":["San Diego, California, United States, 92093"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,8,4]]},"reference":[{"issue":"1","key":"2026081910234426300_cit1","doi-asserted-by":"publisher","first-page":"328","DOI":"10.1016\/S0006-3495(00)76295-3","article-title":"Effect of\nchain length and unsaturation on elasticity of lipid bilayers","volume":"79","author":"Rawicz","year":"2000","journal-title":"Biophys. J."},{"issue":"4","key":"2026081910234426300_cit2","doi-asserted-by":"publisher","first-page":"584","DOI":"10.1021\/cbmi.5c00130","article-title":"Fast Hyperspectral\nand Super-Resolved Mapping of Lipid Membrane Polarity with Single-Molecule\nSensitivity","volume":"4","author":"Pott","year":"2026","journal-title":"Chem. Biomed. Imaging"},{"key":"2026081910234426300_cit3","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1016\/j.ceb.2020.04.001","article-title":"Pay attention\nto membrane tension: Mechanobiology of\nthe cell surface","volume":"66","author":"Sitarska","year":"2020","journal-title":"Curr. Opin. Cell Biol."},{"key":"2026081910234426300_cit4","doi-asserted-by":"publisher","first-page":"1088","DOI":"10.1038\/s41586-025-09222-5","article-title":"NINJ1 regulates plasma\nmembrane fragility under mechanical strain","volume":"644","author":"Zhu","year":"2025","journal-title":"Nature"},{"issue":"14","key":"2026081910234426300_cit5","doi-asserted-by":"publisher","first-page":"2956","DOI":"10.1016\/j.cell.2023.05.033","article-title":"Effective\nmembrane tension: A long-range integrator of cellular dynamics","volume":"186","author":"Keren","year":"2023","journal-title":"Cell"},{"issue":"35","key":"2026081910234426300_cit6","doi-asserted-by":"publisher","first-page":"14379","DOI":"10.1073\/pnas.1111671108","article-title":"Membrane tension\nleads the way","volume":"108","author":"Keren","year":"2011","journal-title":"P. Natl. Acad. Sci. 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Protoc."},{"key":"2026081910234426300_cit10","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1016\/j.sbi.2015.07.010","article-title":"Membrane tension and membrane fusion","volume":"33","author":"Kozlov","year":"2015","journal-title":"Curr. Opin. Struc. 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Cell Biol."},{"issue":"6000","key":"2026081910234426300_cit15","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1126\/science.1193270","article-title":"Piezo1 and\nPiezo2 Are Essential Components of Distinct Mechanically Activated\nCation Channels","volume":"330","author":"Coste","year":"2010","journal-title":"Science"},{"issue":"3","key":"2026081910234426300_cit16","doi-asserted-by":"publisher","first-page":"402","DOI":"10.1016\/j.cell.2010.12.031","article-title":"Cells Respond\nto Mechanical Stress by Rapid Disassembly of Caveolae","volume":"144","author":"Sinha","year":"2011","journal-title":"Cell"},{"issue":"1","key":"2026081910234426300_cit17","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1038\/s41421-020-00233-2","article-title":"Plasma membrane integrity in health\nand disease: significance\nand therapeutic potential","volume":"7","author":"Dias","year":"2021","journal-title":"Cell Discovery"},{"issue":"6","key":"2026081910234426300_cit18","doi-asserted-by":"publisher","first-page":"1063","DOI":"10.1038\/s41592-024-02277-8","article-title":"Dissecting\ncell membrane tension dynamics and its effect on Piezo1-mediated cellular\nmechanosensitivity using force-controlled nanopipettes","volume":"21","author":"Lu\u0308chtefeld","year":"2024","journal-title":"Nat. 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Soc."},{"issue":"11","key":"2026081910234426300_cit25","doi-asserted-by":"publisher","first-page":"1118","DOI":"10.1038\/s41557-018-0127-3","article-title":"A fluorescent membrane tension probe","volume":"10","author":"Colom","year":"2018","journal-title":"Nat. Chem."},{"issue":"8","key":"2026081910234426300_cit26","doi-asserted-by":"publisher","first-page":"3380","DOI":"10.1021\/jacs.8b13189","article-title":"Mechanosensitive\nFluorescent Probes to Image Membrane Tension in Mitochondria, Endoplasmic\nReticulum, and Lysosomes","volume":"141","author":"Goujon","year":"2019","journal-title":"J. Am. Chem. Soc."},{"issue":"35","key":"2026081910234426300_cit27","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202305896","article-title":"A Membrane Tension-Responsive Mechanosensitive DNA Nanomachine","volume":"62","author":"Zheng","year":"2023","journal-title":"Angew. Chem., Int. 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Bioeng."},{"issue":"12","key":"2026081910234426300_cit31","doi-asserted-by":"publisher","first-page":"6068","DOI":"10.1039\/d3cs00565h","article-title":"Multimodal optoacoustic\nimaging: methods and contrast\nmaterials","volume":"53","author":"Chen","year":"2024","journal-title":"Chem. Soc. Rev."},{"issue":"11","key":"2026081910234426300_cit32","doi-asserted-by":"publisher","first-page":"7379","DOI":"10.1021\/acs.chemrev.2c00627","article-title":"Recent Advances in Contrast-Enhanced Photoacoustic Imaging: Overcoming\nthe Physical and Practical Challenges","volume":"123","author":"Choi","year":"2023","journal-title":"Chem.\nRev."},{"issue":"9","key":"2026081910234426300_cit33","doi-asserted-by":"publisher","first-page":"503","DOI":"10.1038\/nphoton.2009.157","article-title":"Multiscale\nphotoacoustic microscopy and computed tomography","volume":"3","author":"Wang","year":"2009","journal-title":"Nat. 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Opt."},{"issue":"38","key":"2026081910234426300_cit36","doi-asserted-by":"publisher","first-page":"21047","DOI":"10.1002\/anie.202109048","article-title":"Boosting Photoacoustic\nEffect via Intramolecular Motions Amplifying Thermal-to-Acoustic Conversion\nEfficiency for Adaptive Image-Guided Cancer Surgery","volume":"60","author":"Gao","year":"2021","journal-title":"Angew. Chem., Int. Ed. Engl."},{"issue":"8","key":"2026081910234426300_cit37","doi-asserted-by":"publisher","first-page":"627","DOI":"10.1038\/nmeth.3925","article-title":"A practical guide\nto photoacoustic tomography in the\nlife sciences","volume":"13","author":"Wang","year":"2016","journal-title":"Nat. Methods"},{"issue":"3","key":"2026081910234426300_cit38","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1038\/nnano.2013.302","article-title":"Semiconducting polymer nanoparticles\nas photoacoustic molecular imaging probes in living mice","volume":"9","author":"Pu","year":"2014","journal-title":"Nat. Nanotechnol."},{"issue":"2","key":"2026081910234426300_cit39","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1006\/ncmn.1993.1016","article-title":"Measurement of total\nneuronal volume, surface area,\nand dendritic length following intracellular physiological recording","volume":"2","author":"Howard","year":"1993","journal-title":"Neuroprotocols"},{"issue":"7","key":"2026081910234426300_cit40","doi-asserted-by":"publisher","first-page":"1601","DOI":"10.1016\/j.cub.2025.02.051","article-title":"Plasma membrane folding enables constant\nsurface area-to-volume ratio in growing mammalian cells","volume":"35","author":"Wu","year":"2025","journal-title":"Curr. Biol."},{"issue":"40","key":"2026081910234426300_cit41","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202309786","article-title":"In Situ\nSelf-Assembled J-Aggregate\nNanofibers of Glycosylated Aza-BODIPY for Synergetic Cell Membrane\nDisruption and Type I Photodynamic Therapy","volume":"62","author":"Liu","year":"2023","journal-title":"Angew. Chem., Int. Ed. Engl."},{"issue":"32","key":"2026081910234426300_cit42","doi-asserted-by":"publisher","first-page":"28651","DOI":"10.1021\/jacs.5c00128","article-title":"Control of Indodicarbocyanine\nDimer Geometry Using Variable-Length Linkers to DNA Scaffolds","volume":"147","author":"Meares","year":"2025","journal-title":"J. Am. Chem. Soc."},{"issue":"1","key":"2026081910234426300_cit43","doi-asserted-by":"publisher","first-page":"5410","DOI":"10.1038\/s41467-021-25452-3","article-title":"Clinically\ntranslatable quantitative molecular photoacoustic\nimaging with liposome-encapsulated ICG J-aggregates","volume":"12","author":"Wood","year":"2021","journal-title":"Nat. Commun."},{"issue":"40","key":"2026081910234426300_cit44","doi-asserted-by":"publisher","first-page":"16464","DOI":"10.1021\/ja305988f","article-title":"Porphyrin Shell Microbubbles\nwith Intrinsic Ultrasound and Photoacoustic Properties","volume":"134","author":"Huynh","year":"2012","journal-title":"J. Am. Chem. Soc."},{"issue":"1","key":"2026081910234426300_cit45","doi-asserted-by":"publisher","first-page":"2376","DOI":"10.1038\/s41467-021-22686-z","article-title":"J-aggregates\nof meso-[2.2]paracyclophanyl-BODIPY\ndye for NIR-II imaging","volume":"12","author":"Li","year":"2021","journal-title":"Nat. Commun"},{"issue":"1","key":"2026081910234426300_cit46","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1021\/ja5111267","article-title":"Fluorogenic\nSquaraine Dimers with Polarity-Sensitive Folding As Bright Far-Red\nProbes for Background-Free Bioimaging","volume":"137","author":"Karpenko","year":"2015","journal-title":"J. Am.\nChem. Soc."},{"issue":"9","key":"2026081910234426300_cit47","doi-asserted-by":"publisher","first-page":"3671","DOI":"10.1073\/pnas.88.9.3671","article-title":"Intracellular Heterogeneity\nin Mitochondrial-Membrane Potentials Revealed by a J-Aggregate-Forming\nLipophilic Cation Jc-1","volume":"88","author":"Smiley","year":"1991","journal-title":"P. Natl. Acad. Sci.\nU.S.A."},{"issue":"38","key":"2026081910234426300_cit48","doi-asserted-by":"publisher","first-page":"13394","DOI":"10.1002\/anie.201907754","article-title":"Stable J-Aggregation\nof an aza-BODIPY-Lipid in a Liposome for Optical Cancer Imaging","volume":"58","author":"Cheng","year":"2019","journal-title":"Angew. Chem. Int. Ed."},{"issue":"4","key":"2026081910234426300_cit49","doi-asserted-by":"publisher","first-page":"324","DOI":"10.1038\/nmat2986","article-title":"Porphysome\nnanovesicles generated by porphyrin bilayers for use as\nmultimodal biophotonic contrast agents","volume":"10","author":"Lovell","year":"2011","journal-title":"Nat.\nMater."},{"issue":"11","key":"2026081910234426300_cit50","doi-asserted-by":"publisher","first-page":"4970","DOI":"10.1021\/jacs.9b13219","article-title":"Water-Soluble\nBODIPY Photocages with Tunable Cellular Localization","volume":"142","author":"Kand","year":"2020","journal-title":"J. Am. Chem. 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