{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T18:42:13Z","timestamp":1785436933573,"version":"3.56.0"},"posted":{"date-parts":[[2026,3,31]]},"group-title":"Cell Biology","reference-count":50,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T00:00:00Z","timestamp":1774915200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"award":["R35GM128747"],"award-info":[{"award-number":["R35GM128747"]}],"id":[{"id":"https:\/\/ror.org\/04q48ey07","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000001","name":"U.S. National Science Foundation","doi-asserted-by":"crossref","award":["2204447"],"award-info":[{"award-number":["2204447"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,3,31]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Platelets are blood cells that play a critical role in hemostasis and thrombosis. Serum albumin, which constitutes approximately 50% of plasma proteins, has traditionally been considered non-interactive with platelets and not involved in platelet function. Here, using a molecular force sensor and platelet adhesion and aggregation assays, we show that serum albumin, if denatured, specifically binds to integrin \u03b1\n                  <jats:sub>IIb<\/jats:sub>\n                  \u03b2\n                  <jats:sub>3<\/jats:sub>\n                  in platelets and transmits platelet contractile forces, regulating platelet activation, adhesion and aggregation as effectively as fibrinogen (the clotting factor I). 0.1% ethanol or 10 \u00b5M hydrogen peroxide, physiologically attainable in blood through alcohol intake or disease-elevated oxidative stress, are sufficient to denature albumin into a functional platelet ligand. These findings revealed albumin as a previously unrecognized but important regulator of platelet functions, with broad implications for the thrombotic risk in the context of physiological conditions that induce albumin denaturation.\n                <\/jats:p>","DOI":"10.64898\/2026.03.30.715112","type":"posted-content","created":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T18:40:41Z","timestamp":1774982441000},"source":"Crossref","is-referenced-by-count":0,"title":["Denatured Albumin Gains a Function of Regulating Platelet Activity"],"prefix":"10.64898","author":[{"given":"Vivek","family":"Pandey","sequence":"first","affiliation":[{"name":"Hoxworth Blood Center, College of Medicine, University of Cincinnati, Cincinnati, OH, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Subhankar","family":"Kundu","sequence":"additional","affiliation":[{"name":"Hoxworth Blood Center, College of Medicine, University of Cincinnati, Cincinnati, OH, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah J","family":"Wang","sequence":"additional","affiliation":[{"name":"Hoxworth Blood Center, College of Medicine, University of Cincinnati, Cincinnati, OH, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arghajit","family":"Pyne","sequence":"additional","affiliation":[{"name":"Hoxworth Blood Center, College of Medicine, University of Cincinnati, Cincinnati, OH, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Long","family":"Que","sequence":"additional","affiliation":[{"name":"Department of Electrical and Computer Engineering, Iowa State University, Ames, IA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3301-3196","authenticated-orcid":false,"given":"Xuefeng","family":"Wang","sequence":"additional","affiliation":[{"name":"Hoxworth Blood Center, College of Medicine, University of Cincinnati, Cincinnati, OH, USA"},{"name":"The department of Pathology and Laboratory Medicine, College of Medicine, University of Cincinnati, Cincinnati, OH, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026040309000638000_2026.03.30.715112v1.1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tmrv.2009.09.005"},{"key":"2026040309000638000_2026.03.30.715112v1.2","doi-asserted-by":"crossref","first-page":"3192","DOI":"10.1002\/acn3.52227","article-title":"Identification of fibrinogen as a plasma protein binding partner for lecanemab biosimilar IgG","volume":"11","year":"2024","journal-title":"Ann Clin Transl Neur"},{"key":"2026040309000638000_2026.03.30.715112v1.3","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(88)90567-3"},{"key":"2026040309000638000_2026.03.30.715112v1.4","first-page":"3011","article-title":"The GPIIb\/IIIa (integrin \u03b1IIb\u03b23) odyssey: a technology-driven saga of a receptor with twists, turns, and even a bend. Blood","volume":"112","year":"2008","journal-title":"The Journal of the American Society of Hematology"},{"key":"2026040309000638000_2026.03.30.715112v1.5","doi-asserted-by":"crossref","unstructured":"Nieswandt, B. et al. Glycoprotein VI but not \u03b12\u03b21 integrin is essential for platelet interaction with collagen. The EMBO journal (2001).","DOI":"10.1093\/emboj\/20.9.2120"},{"key":"2026040309000638000_2026.03.30.715112v1.6","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2002-12-3882"},{"key":"2026040309000638000_2026.03.30.715112v1.7","doi-asserted-by":"publisher","DOI":"10.1213\/ANE.0b013e31822e1853"},{"key":"2026040309000638000_2026.03.30.715112v1.8","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.117.308564"},{"key":"2026040309000638000_2026.03.30.715112v1.9","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.12.6711"},{"key":"2026040309000638000_2026.03.30.715112v1.10","doi-asserted-by":"crossref","unstructured":"Merlot, A.M. , Kalinowski, D.S. & Richardson, D.R . Unraveling the mysteries of serum albumin-more than just a serum protein. Front Physiol 5 (2014).","DOI":"10.3389\/fphys.2014.00299"},{"key":"2026040309000638000_2026.03.30.715112v1.11","doi-asserted-by":"publisher","DOI":"10.1163\/156856292X00196"},{"key":"2026040309000638000_2026.03.30.715112v1.12","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.11.001"},{"key":"2026040309000638000_2026.03.30.715112v1.13","doi-asserted-by":"publisher","DOI":"10.1002\/jbm.820250311"},{"key":"2026040309000638000_2026.03.30.715112v1.14","doi-asserted-by":"crossref","first-page":"1823","DOI":"10.1111\/j.1538-7836.2004.00925.x","article-title":"Evaluation of the role of platelet integrins in fibronectin-dependent spreading and adhesion","volume":"2","year":"2004","journal-title":"Journal of thrombosis and haemostasis"},{"key":"2026040309000638000_2026.03.30.715112v1.15","doi-asserted-by":"publisher","DOI":"10.1163\/156856291X00133"},{"key":"2026040309000638000_2026.03.30.715112v1.16","doi-asserted-by":"crossref","first-page":"1036","DOI":"10.1016\/j.biomaterials.2009.10.017","article-title":"The adherence of platelets to adsorbed albumin by receptor-mediated recognition of binding sites exposed by adsorption-induced unfolding","volume":"31","year":"2010","journal-title":"Biomaterials"},{"key":"2026040309000638000_2026.03.30.715112v1.17","doi-asserted-by":"crossref","unstructured":"Hylton, D.M. , Shalaby, S.W. & Latour, R. J.r. Direct correlation between adsorption-induced changes in protein structure and platelet adhesion. J Biomed Mater Res A 73a, 349\u2013358 (2005).","DOI":"10.1002\/jbm.a.30295"},{"key":"2026040309000638000_2026.03.30.715112v1.18","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V82.1.135.bloodjournal821135"},{"key":"2026040309000638000_2026.03.30.715112v1.19","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2014-11-607614"},{"key":"2026040309000638000_2026.03.30.715112v1.20","doi-asserted-by":"publisher","DOI":"10.1016\/0022-1759(87)90214-6"},{"key":"2026040309000638000_2026.03.30.715112v1.21","doi-asserted-by":"crossref","first-page":"1461","DOI":"10.1111\/j.1538-7836.2006.01943.x","article-title":"Role of fibronectin assembly in platelet thrombus formation","volume":"4","year":"2006","journal-title":"Journal of Thrombosis and Haemostasis"},{"key":"2026040309000638000_2026.03.30.715112v1.22","doi-asserted-by":"crossref","first-page":"2967","DOI":"10.1182\/blood.V88.8.2967.bloodjournal8882967","article-title":"Adhesion of platelets to surface-bound fibrinogen under flow","volume":"88","year":"1996","journal-title":"Blood"},{"key":"2026040309000638000_2026.03.30.715112v1.23","doi-asserted-by":"crossref","unstructured":"Heggestad, J.T. , Fontes, C.M. , Joh, D.Y. , Hucknall, A.M. & Chilkoti, A . In Pursuit of Zero 2.0: Recent Developments in Nonfouling Polymer Brushes for Immunoassays. Adv Mater 32 (2020).","DOI":"10.1002\/adma.201903285"},{"key":"2026040309000638000_2026.03.30.715112v1.24","doi-asserted-by":"crossref","unstructured":"Kapp, T.G. et al. A Comprehensive Evaluation of the Activity and Selectivity Profile of Ligands for RGD-binding Integrins. Sci Rep-Uk 7 (2017).","DOI":"10.1038\/srep39805"},{"key":"2026040309000638000_2026.03.30.715112v1.25","doi-asserted-by":"crossref","unstructured":"Rana, A. , Westein, E. , Niego, B. & Hagemeyer, C.E . Shear-Dependent Platelet Aggregation: Mechanisms and Therapeutic Opportunities. Front Cardiovasc Med 6, 141 (2019).","DOI":"10.3389\/fcvm.2019.00141"},{"key":"2026040309000638000_2026.03.30.715112v1.26","doi-asserted-by":"crossref","unstructured":"Kundu, S. , Pal, K. , Pyne, A. & Wang, X.F . Force-bearing phagocytic adhesion rings mediate the phagocytosis of surface-bound particles. Nat Commun 16 (2025).","DOI":"10.1038\/s41467-025-56404-w"},{"key":"2026040309000638000_2026.03.30.715112v1.27","doi-asserted-by":"crossref","first-page":"4386","DOI":"10.1016\/j.cub.2022.08.040","article-title":"Filopodial adhesive force in discrete nodes revealed by integrin molecular tension imaging","volume":"32","year":"2022","journal-title":"Curr Biol"},{"key":"2026040309000638000_2026.03.30.715112v1.28","doi-asserted-by":"publisher","DOI":"10.1016\/j.bios.2017.09.007"},{"key":"2026040309000638000_2026.03.30.715112v1.29","doi-asserted-by":"crossref","first-page":"11156","DOI":"10.1021\/acs.nanolett.5c02578","article-title":"Characterizing Integrin Tensions during Platelet Adhesion and Stiffness Sensing","volume":"25","year":"2025","journal-title":"Nano Lett"},{"key":"2026040309000638000_2026.03.30.715112v1.30","doi-asserted-by":"publisher","DOI":"10.1126\/science.1231041"},{"key":"2026040309000638000_2026.03.30.715112v1.31","first-page":"192","article-title":"Chemical structures and mode of action of intravenous glycoprotein IIb\/IIIa receptor blockers: A review","volume":"13","year":"2008","journal-title":"Exp Clin Cardiol"},{"key":"2026040309000638000_2026.03.30.715112v1.32","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.109.882746"},{"key":"2026040309000638000_2026.03.30.715112v1.33","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.98.11.1085"},{"key":"2026040309000638000_2026.03.30.715112v1.34","doi-asserted-by":"publisher","DOI":"10.1172\/JCI26989"},{"key":"2026040309000638000_2026.03.30.715112v1.35","doi-asserted-by":"crossref","unstructured":"Bledzka, K. , Qin, J. & Plow, E.F . Integrin \u03b1IIb\u03b23. Platelets, 227\u2013241 (2019).","DOI":"10.1016\/B978-0-12-813456-6.00012-6"},{"key":"2026040309000638000_2026.03.30.715112v1.36","doi-asserted-by":"publisher","DOI":"10.1038\/nmat2903"},{"key":"2026040309000638000_2026.03.30.715112v1.37","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpj.2022.11.013"},{"key":"2026040309000638000_2026.03.30.715112v1.38","doi-asserted-by":"crossref","first-page":"26","DOI":"10.7812\/TPP\/09-145","article-title":"The limits of tolerance: convicted alcohol-impaired drivers share experiences driving under the influence","volume":"14","year":"2010","journal-title":"Perm J"},{"key":"2026040309000638000_2026.03.30.715112v1.39","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2017.12.021"},{"key":"2026040309000638000_2026.03.30.715112v1.40","doi-asserted-by":"crossref","first-page":"1042","DOI":"10.1089\/ars.2012.4817","article-title":"Hydrogen Peroxide Sensing and Signaling by Protein Kinases in the Cardiovascular System","volume":"18","year":"2013","journal-title":"Antioxid Redox Sign"},{"key":"2026040309000638000_2026.03.30.715112v1.41","doi-asserted-by":"publisher","DOI":"10.1016\/J.ABB.2016.05.005"},{"key":"2026040309000638000_2026.03.30.715112v1.42","doi-asserted-by":"crossref","unstructured":"Erana, H. et al. A Protein Misfolding Shaking Amplification-based method for the spontaneous generation of hundreds of bona fide prions. Nat Commun 15, 2112 (2024).","DOI":"10.1038\/s41467-024-46360-2"},{"key":"2026040309000638000_2026.03.30.715112v1.43","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M401764200"},{"key":"2026040309000638000_2026.03.30.715112v1.44","doi-asserted-by":"crossref","unstructured":"Mishra, V. & Heath, R.J . Structural and Biochemical Features of Human Serum Albumin Essential for Eukaryotic Cell Culture. Int J Mol Sci 22 (2021).","DOI":"10.3390\/ijms22168411"},{"key":"2026040309000638000_2026.03.30.715112v1.45","doi-asserted-by":"crossref","first-page":"C531","DOI":"10.1152\/ajpcell.00431.2004","article-title":"Degradation of oxidative stress-induced denatured albumin in rat liver endothelial cells","volume":"289","year":"2005","journal-title":"Am J Physiol-Cell Ph"},{"key":"2026040309000638000_2026.03.30.715112v1.46","doi-asserted-by":"crossref","unstructured":"Paar, M. , et al. Albumin in patients with liver disease shows an altered conformation. Commun Biol 4 (2021).","DOI":"10.1038\/s42003-021-02269-w"},{"key":"2026040309000638000_2026.03.30.715112v1.47","doi-asserted-by":"crossref","unstructured":"Tsao, F.H.C. & Meyer, K.C . Human Serum Albumin Misfolding in Aging and Disease. Int J Mol Sci 23 (2022).","DOI":"10.3390\/ijms231911675"},{"key":"2026040309000638000_2026.03.30.715112v1.48","doi-asserted-by":"crossref","unstructured":"Walter, E.J. , Hanna-Jumma, S. , Carraretto, M. & Forni, L . The pathophysiological basis and consequences of fever. Crit Care 20, 200 (2016).","DOI":"10.1186\/s13054-016-1375-5"},{"key":"2026040309000638000_2026.03.30.715112v1.49","doi-asserted-by":"publisher","DOI":"10.1021\/jp409936v"},{"key":"2026040309000638000_2026.03.30.715112v1.50","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2008.05.052"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.64898\/2026.03.30.715112","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T16:00:14Z","timestamp":1775232014000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.64898\/2026.03.30.715112"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,31]]},"references-count":50,"URL":"https:\/\/doi.org\/10.64898\/2026.03.30.715112","relation":{},"subject":[],"published":{"date-parts":[[2026,3,31]]},"subtype":"preprint"}}