{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T14:01:45Z","timestamp":1780408905848,"version":"3.54.1"},"reference-count":27,"publisher":"AIP Publishing","issue":"6","funder":[{"DOI":"10.13039\/100006501","name":"Cystic Fibrosis Foundation Therapeutics","doi-asserted-by":"publisher","award":["SUPERf2020G0"],"award-info":[{"award-number":["SUPERf2020G0"]}],"id":[{"id":"10.13039\/100006501","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006501","name":"Cystic Fibrosis Foundation Therapeutics","doi-asserted-by":"publisher","award":["HILL20Y2-OUT"],"award-info":[{"award-number":["HILL20Y2-OUT"]}],"id":[{"id":"10.13039\/100006501","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006501","name":"Cystic Fibrosis Foundation Therapeutics","doi-asserted-by":"publisher","award":["SUPERf2022G0"],"award-info":[{"award-number":["SUPERf2022G0"]}],"id":[{"id":"10.13039\/100006501","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["pubs.aip.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,6,1]]},"abstract":"<jats:p>Molecular adhesion plays a central role in many biological systems, yet existing methods to quantify adhesive strength often struggle to bridge the gap between single-molecule resolution and biologically relevant environments. Here, we present a scalable micromagnetic bead-based adhesion assay capable of quantifying detachment forces under physiologically meaningful conditions. Designed to probe mucoadhesion in the context of mucociliary clearance, our system applies controlled magnetic forces to ligand-coated beads adhered to functionalized substrates and tracks detachment events using high-speed microscopy and calibrated z-displacement mapping. The platform combines control of substrate and bead surface chemistry with high-throughput imaging and in situ force calibration via Stokes drag. We demonstrate the ability to distinguish sub-nanonewton to nanonewton force regimes across a range of bead\u2013substrate pairings, including carboxyl\u2013carboxyl, polyethylene glycol\u2013polyethylene glycol, and cell culture-derived human bronchial epithelial mucus interactions. Surface functionalization was validated via fluorescence imaging and zeta potential measurements, while detachment forces were used to estimate binding energy and infer dissociation constants. This assay enables detailed characterization of multivalent, force-sensitive adhesive interactions and offers a powerful new approach to studying bioadhesive systems, including mucus\u2013pathogen interactions and drug delivery materials.<\/jats:p>","DOI":"10.1063\/5.0293707","type":"journal-article","created":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T13:00:57Z","timestamp":1780405257000},"update-policy":"https:\/\/doi.org\/10.1063\/aip-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["Molecular adhesion assay for biopolymer systems"],"prefix":"10.1063","volume":"97","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9725-1209","authenticated-orcid":false,"given":"Jeremy A.","family":"Cribb","sequence":"first","affiliation":[{"name":"Department of Physics and Astronomy, The University of North Carolina at Chapel Hill 1 , Chapel Hill, North Carolina 27599,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6133-5264","authenticated-orcid":false,"given":"Farnaz","family":"Fazelpour","sequence":"additional","affiliation":[{"name":"Marsico Lung Institute, The University of North Carolina at Chapel Hill 2 , Chapel Hill, North Carolina 27599,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-1334-1475","authenticated-orcid":false,"given":"David A.","family":"Wollensak","sequence":"additional","affiliation":[{"name":"Department of Physics and Astronomy, The University of North Carolina at Chapel Hill 1 , Chapel Hill, North Carolina 27599,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danielle","family":"Rice","sequence":"additional","affiliation":[{"name":"College of Engineering, North Carolina Agricultural and Technical State University 3 , Greensboro, North Carolina 27411,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Max","family":"deJong","sequence":"additional","affiliation":[{"name":"Department of Physics and Astronomy, The University of North Carolina at Chapel Hill 1 , Chapel Hill, North Carolina 27599,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9270-777X","authenticated-orcid":false,"given":"David","family":"Hill","sequence":"additional","affiliation":[{"name":"Department of Physics and Astronomy, The University of North Carolina at Chapel Hill 1 , Chapel Hill, North Carolina 27599,","place":["USA"]},{"name":"Marsico Lung Institute, The University of North Carolina at Chapel Hill 2 , Chapel Hill, North Carolina 27599,","place":["USA"]},{"name":"Lampe Joint Department of Biomedical Engineering, The University of North Carolina at Chapel Hill 4 , Chapel Hill, North Carolina 27599,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2569-071X","authenticated-orcid":false,"given":"Richard","family":"Superfine","sequence":"additional","affiliation":[{"name":"Department of Applied Physical Sciences, The University of North Carolina at Chapel Hill 5 , Chapel Hill, North Carolina 27599,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"317","published-online":{"date-parts":[[2026,6,2]]},"reference":[{"issue":"16","key":"2026060209005058100_c1","doi-asserted-by":"publisher","first-page":"163001","DOI":"10.1088\/0022-3727\/41\/16\/163001","article-title":"Adhesive elastic contacts: JKR and more","volume":"41","year":"2008","journal-title":"J.\u00a0Phys. D: Appl. Phys."},{"issue":"18","key":"2026060209005058100_c2","doi-asserted-by":"publisher","first-page":"2200211","DOI":"10.1002\/admi.202200211","article-title":"Recent advances in mucoadhesive interface materials, mucoadhesion characterization, and technologies","volume":"9","year":"2022","journal-title":"Adv. Mater. Interfaces"},{"issue":"4","key":"2026060209005058100_c3","doi-asserted-by":"publisher","first-page":"167","DOI":"10.3109\/09687689709044318","article-title":"Cell adhesion: More than just glue (review)","volume":"15","year":"1998","journal-title":"Mol. Membr. Biol."},{"issue":"49","key":"2026060209005058100_c4","doi-asserted-by":"publisher","first-page":"12501","DOI":"10.1073\/pnas.1811787115","article-title":"Roles of mucus adhesion and cohesion in cough clearance","volume":"115","year":"2018","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"issue":"5","key":"2026060209005058100_c5","doi-asserted-by":"publisher","first-page":"L910","DOI":"10.1152\/ajplung.00274.2018","article-title":"Buffer drains and mucus is transported upward in a tilted mucus clearance assay","volume":"315","year":"2018","journal-title":"Am. J. Physiol. Lung Cell. Mol. Physiol."},{"issue":"4","key":"2026060209005058100_c6","doi-asserted-by":"publisher","first-page":"215","DOI":"10.4103\/2231-4040.90876","article-title":"A review on mucoadhesive polymer used in nasal drug delivery system","volume":"2","year":"2011","journal-title":"J.\u00a0Adv. Pharm. Technol. Res."},{"issue":"151","key":"2026060209005058100_c7","doi-asserted-by":"publisher","first-page":"20180738","DOI":"10.1098\/rsif.2018.0738","article-title":"The role of adhesion in contact mechanics","volume":"16","year":"2019","journal-title":"J.\u00a0R. Soc. Interface"},{"issue":"4","key":"2026060209005058100_c8","doi-asserted-by":"publisher","first-page":"e0175323","DOI":"10.1371\/journal.pone.0175323","article-title":"Interactions between the breast cancer-associated MUC1 mucins and C-type lectin characterized by optical tweezers","volume":"12","year":"2017","journal-title":"PLoS One"},{"issue":"5","key":"2026060209005058100_c9","doi-asserted-by":"publisher","first-page":"479","DOI":"10.1111\/joim.12910","article-title":"Mucus and mucins in diseases of the intestinal and respiratory tracts","volume":"285","year":"2019","journal-title":"J.\u00a0Intern. Med."},{"issue":"5","key":"2026060209005058100_c10","doi-asserted-by":"publisher","first-page":"524","DOI":"10.1093\/glycob\/cwu183","article-title":"Single molecule study of heterotypic interactions between mucins possessing the Tn cancer antigen","volume":"25","year":"2015","journal-title":"Glycobiology"},{"key":"2026060209005058100_c11","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1007\/978-1-61779-513-8_15","article-title":"Establishment of respiratory air-liquid interface cultures and their use in studying mucin production, secretion, and function","volume":"842","year":"2012","journal-title":"Methods Mol. Biol."},{"issue":"4","key":"2026060209005058100_c12","doi-asserted-by":"publisher","first-page":"1757","DOI":"10.1152\/physrev.00004.2021","article-title":"Physiology and pathophysiology of human airway mucus","volume":"102","year":"2022","journal-title":"Physiol. Rev."},{"issue":"5","key":"2026060209005058100_c13","doi-asserted-by":"publisher","first-page":"2191","DOI":"10.1016\/s0006-3495(93)81277-3","article-title":"Relationship between receptor\/ligand binding affinity and adhesion strength","volume":"65","year":"1993","journal-title":"Biophys. J."},{"issue":"1","key":"2026060209005058100_c14","doi-asserted-by":"publisher","first-page":"517","DOI":"10.1016\/s0006-3495(97)78090-1","article-title":"Simulation of detachment of specifically bound particles from surfaces by shear flow","volume":"73","year":"1997","journal-title":"Biophys. J."},{"issue":"2","key":"2026060209005058100_c15","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1016\/j.addr.2008.09.012","article-title":"Micro- and macrorheology of mucus","volume":"61","year":"2009","journal-title":"Adv. Drug Delivery Rev."},{"issue":"5","key":"2026060209005058100_c16","doi-asserted-by":"publisher","first-page":"053905","DOI":"10.1063\/1.4719916","article-title":"High-force NdFeB-based magnetic tweezers device optimized for microrheology experiments","volume":"83","year":"2012","journal-title":"Rev. Sci. Instrum."},{"issue":"8","key":"2026060209005058100_c17","doi-asserted-by":"publisher","first-page":"1600534","DOI":"10.1002\/mabi.201600534","article-title":"Innovative methods and applications in mucoadhesion research","volume":"17","year":"2017","journal-title":"Macromol. Biosci."},{"issue":"6936","key":"2026060209005058100_c18","doi-asserted-by":"publisher","first-page":"190","DOI":"10.1038\/nature01605","article-title":"Direct observation of catch bonds involving cell-adhesion molecules","volume":"423","year":"2003","journal-title":"Nature"},{"issue":"12","key":"2026060209005058100_c19","doi-asserted-by":"publisher","first-page":"2279","DOI":"10.1016\/j.bpj.2018.10.021","article-title":"Force spectroscopy and beyond: Innovations and opportunities","volume":"115","year":"2018","journal-title":"Biophys. J."},{"issue":"2","key":"2026060209005058100_c20","doi-asserted-by":"publisher","first-page":"691","DOI":"10.1152\/physrev.00004.2010","article-title":"Tissue organization by cadherin adhesion molecules: Dynamic molecular and cellular mechanisms of morphogenetic regulation","volume":"91","year":"2011","journal-title":"Physiol. Rev."},{"issue":"2","key":"2026060209005058100_c21","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1016\/j.yexcr.2019.03.036","article-title":"The inner life of integrin adhesion sites: From single molecules to functional macromolecular complexes","volume":"379","year":"2019","journal-title":"Exp. Cell Res."},{"issue":"1","key":"2026060209005058100_c22","doi-asserted-by":"publisher","first-page":"9660","DOI":"10.1038\/s41598-018-28047-z","article-title":"Influencing the adhesion properties and wettability of mucin protein films by variation of the environmental pH","volume":"8","year":"2018","journal-title":"Sci. Rep."},{"issue":"1","key":"2026060209005058100_c23","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1021\/acsinfecdis.5b00108","article-title":"Using computational modeling to optimize the design of antibodies that trap viruses in mucus","volume":"2","year":"2016","journal-title":"ACS Infect. Dis."},{"issue":"4","key":"2026060209005058100_c24","doi-asserted-by":"publisher","first-page":"1681","DOI":"10.1021\/nl200189w","article-title":"Imaginary magnetic tweezers for massively parallel surface adhesion spectroscopy","volume":"11","year":"2011","journal-title":"Nano Lett."},{"issue":"2","key":"2026060209005058100_c25","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1016\/j.chom.2016.01.001","article-title":"The interaction between respiratory pathogens and mucus","volume":"19","year":"2016","journal-title":"Cell Host Microbe"},{"issue":"20","key":"2026060209005058100_c26","doi-asserted-by":"publisher","first-page":"e4534","DOI":"10.21769\/BioProtoc.4534","article-title":"Single-molecule force spectroscopy on biomembrane force probe to characterize force-dependent bond lifetimes of receptor-ligand interactions on living cells","volume":"12","year":"2022","journal-title":"Bio-Protoc."},{"issue":"1","key":"2026060209005058100_c27","doi-asserted-by":"publisher","first-page":"416","DOI":"10.1021\/la203638g","article-title":"How to prepare reproducible, homogeneous, and hydrolytically stable aminosilane-derived layers on silica","volume":"28","year":"2012","journal-title":"Langmuir"}],"container-title":["Review of Scientific Instruments"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.aip.org\/aip\/rsi\/article-pdf\/doi\/10.1063\/5.0293707\/21024975\/063703_1_5.0293707.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.aip.org\/aip\/rsi\/article-pdf\/doi\/10.1063\/5.0293707\/21024975\/063703_1_5.0293707.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T13:00:58Z","timestamp":1780405258000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.aip.org\/rsi\/article\/97\/6\/063703\/3393523\/Molecular-adhesion-assay-for-biopolymer-systems"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,1]]},"references-count":27,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2026,6,1]]}},"URL":"https:\/\/doi.org\/10.1063\/5.0293707","relation":{},"ISSN":["0034-6748","1089-7623"],"issn-type":[{"value":"0034-6748","type":"print"},{"value":"1089-7623","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,6]]},"published":{"date-parts":[[2026,6,1]]},"article-number":"063703"}}