{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T11:38:37Z","timestamp":1785411517834,"version":"3.56.0"},"posted":{"date-parts":[[2026,7,2]]},"group-title":"Bioengineering","reference-count":41,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T00:00:00Z","timestamp":1782950400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"award":["HL161499"],"award-info":[{"award-number":["HL161499"]}],"id":[{"id":"https:\/\/ror.org\/012pb6c26","id-type":"ROR","asserted-by":"publisher"}]},{"award":["HL136927"],"award-info":[{"award-number":["HL136927"]}],"id":[{"id":"https:\/\/ror.org\/012pb6c26","id-type":"ROR","asserted-by":"publisher"}]},{"award":["HL091842"],"award-info":[{"award-number":["HL091842"]}],"id":[{"id":"https:\/\/ror.org\/012pb6c26","id-type":"ROR","asserted-by":"publisher"}]},{"award":["EB033395"],"award-info":[{"award-number":["EB033395"]}],"id":[{"id":"https:\/\/ror.org\/00372qc85","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000897","name":"Cystic Fibrosis Foundation","doi-asserted-by":"crossref","award":["003140I221"],"award-info":[{"award-number":["003140I221"]}],"id":[{"id":"10.13039\/100000897","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,7,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  A wide spectrum of microparticles is inhaled with each breath, deposited on airway surfaces, entrapped in the mucus, and removed by mucociliary transport (MCT). However, the influence of particle size on MCT remains largely unknown. Here, we investigated the MCT of microparticles with a trachea-on-a-chip method that integrates a micro-machined device with a trachea explant from newborn pigs. This method preserves airway structures for mucus secretion and cilia beating (\n                  <jats:italic>e.g.,<\/jats:italic>\n                  airway surface epithelia and submucosal glands), maintains physiological air-liquid-interface on the airway surface, and allows tracks motion of microparticles with high resolution. Using this method, we found that, in normal airways, 6 \u00b5m polystyrene particles clear rapidly, whereas 102 \u00b5m particles clear slower and require mucus strands for motion. In cystic fibrosis (CF) airways, MCT of microparticles reduces, but particle size-dependence persists. Methacholine increases particle motion in normal airways, but not in CF airways. These findings suggest two distinct MCT processes, in which large particles rely on mucus strands for clearance, small particles can be cleared independent of mucus strands, and CF disrupts both.\n                <\/jats:p>\n                <jats:sec>\n                  <jats:title>Abstract Figure<\/jats:title>\n                  <jats:fig id=\"ufig1\" position=\"float\" orientation=\"portrait\" fig-type=\"figure\">\n                    <jats:label>Graphical Abstract<\/jats:label>\n                    <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"735890v1_ufig1\" position=\"float\" orientation=\"portrait\"\/>\n                  <\/jats:fig>\n                <\/jats:sec>","DOI":"10.64898\/2026.07.01.735890","type":"posted-content","created":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T12:05:40Z","timestamp":1782993940000},"source":"Crossref","is-referenced-by-count":0,"title":["Particle size determines mucociliary transport mechanisms in normal and cystic fibrosis airways"],"prefix":"10.64898","author":[{"given":"Michael","family":"Scott","sequence":"first","affiliation":[{"name":"Roy J. Carver Department of Biomedical Engineering, College of Engineering, University of Iowa, USA"},{"name":"Pappajohn Biomedical Institute, University of Iowa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaleb C.","family":"Bierstedt","sequence":"additional","affiliation":[{"name":"Roy J. Carver Department of Biomedical Engineering, College of Engineering, University of Iowa, USA"},{"name":"Pappajohn Biomedical Institute, University of Iowa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weijie","family":"Du","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Carver College of Medicine, University of Iowa, USA"},{"name":"Pappajohn Biomedical Institute, University of Iowa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitchell J.","family":"Riley","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Carver College of Medicine, University of Iowa, USA"},{"name":"Pappajohn Biomedical Institute, University of Iowa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony J.","family":"Fischer","sequence":"additional","affiliation":[{"name":"Stead Family Department of Pediatrics, Carver College of Medicine, University of Iowa, USA"},{"name":"Pappajohn Biomedical Institute, University of Iowa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuliang","family":"Xie","sequence":"additional","affiliation":[{"name":"Roy J. Carver Department of Biomedical Engineering, College of Engineering, University of Iowa, USA"},{"name":"Pappajohn Biomedical Institute, University of Iowa"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026070601550942000_2026.07.01.735890v1.1","doi-asserted-by":"publisher","DOI":"10.1016\/0021-8502(86)90035-2"},{"issue":"4","key":"2026070601550942000_2026.07.01.735890v1.2","first-page":"337","article-title":"Deposition, retention, and clearance of inhaled particles","volume":"37","year":"1980","journal-title":"Br J Ind Med"},{"key":"2026070601550942000_2026.07.01.735890v1.3","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.154.6.8970383"},{"key":"2026070601550942000_2026.07.01.735890v1.4","doi-asserted-by":"publisher","DOI":"10.1126\/science.1255825"},{"key":"2026070601550942000_2026.07.01.735890v1.5","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra0910061"},{"key":"2026070601550942000_2026.07.01.735890v1.6","doi-asserted-by":"publisher","DOI":"10.1513\/AnnalsATS.201805-308AW"},{"key":"2026070601550942000_2026.07.01.735890v1.7","doi-asserted-by":"publisher","DOI":"10.1002\/ppul.10079"},{"key":"2026070601550942000_2026.07.01.735890v1.8","doi-asserted-by":"publisher","DOI":"10.1016\/j.scitotenv.2024.170004"},{"issue":"2","key":"2026070601550942000_2026.07.01.735890v1.9","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1542\/peds.60.2.146","article-title":"Effects of gravity on tracheal mucus transport rates in normal subjects and in patients with cystic fibrosis","volume":"60","year":"1977","journal-title":"Pediatrics"},{"key":"2026070601550942000_2026.07.01.735890v1.10","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2125.2003.01892.x"},{"issue":"1","key":"2026070601550942000_2026.07.01.735890v1.11","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1080\/17425247.2016.1206074","article-title":"Emerging delivery platforms for mucosal administration of biopharmaceuticals: a critical update on nasal, pulmonary and oral routes","volume":"14","year":"2017","journal-title":"Expert Opin Drug Deliv"},{"issue":"6","key":"2026070601550942000_2026.07.01.735890v1.12","first-page":"733","article-title":"Tracheal mucociliary transport in patients with cystic fibrosis and its stimulation by terbutaline","volume":"111","year":"1975","journal-title":"Am Rev Respir Dis"},{"key":"2026070601550942000_2026.07.01.735890v1.13","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1323633111"},{"key":"2026070601550942000_2026.07.01.735890v1.14","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00024.2015"},{"issue":"2","key":"2026070601550942000_2026.07.01.735890v1.15","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1208\/s12249-008-9072-6","article-title":"Embryonic chicken trachea as a new in vitro model for the investigation of mucociliary particle clearance in the airways","volume":"9","year":"2008","journal-title":"AAPS PharmSciTech"},{"key":"2026070601550942000_2026.07.01.735890v1.16","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2011.12.015"},{"key":"2026070601550942000_2026.07.01.735890v1.17","doi-asserted-by":"crossref","unstructured":"Fischer, A.J. , et al., Mucus strands from submucosal glands initiate mucociliary transport of large particles. JCI Insight, 2019. 4(1).","DOI":"10.1172\/jci.insight.124863"},{"key":"2026070601550942000_2026.07.01.735890v1.18","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.90203.2008"},{"issue":"12","key":"2026070601550942000_2026.07.01.735890v1.19","doi-asserted-by":"crossref","first-page":"3093","DOI":"10.1039\/D4LC00134F","article-title":"Dynamic measurement of airway surface liquid volume with an ex vivo trachea-chip","volume":"24","year":"2024","journal-title":"Lab on a Chip"},{"issue":"2","key":"2026070601550942000_2026.07.01.735890v1.20","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1152\/jappl.1988.65.2.971","article-title":"Stimulation of ciliary beat frequency by autonomic agonists: in vivo","volume":"65","year":"1988","journal-title":"J Appl Physiol (1985)"},{"key":"2026070601550942000_2026.07.01.735890v1.21","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00174.2002"},{"key":"2026070601550942000_2026.07.01.735890v1.22","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1703228114"},{"key":"2026070601550942000_2026.07.01.735890v1.23","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2017.08.113"},{"key":"2026070601550942000_2026.07.01.735890v1.24","doi-asserted-by":"crossref","unstructured":"Xie, Y. , et al., Acidic submucosal gland pH and elevated protein concentration produce abnormal cystic fibrosis mucus. Dev Cell, 2020.","DOI":"10.1016\/j.devcel.2020.07.002"},{"key":"2026070601550942000_2026.07.01.735890v1.25","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(00)80284-1"},{"key":"2026070601550942000_2026.07.01.735890v1.26","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80570-X"},{"key":"2026070601550942000_2026.07.01.735890v1.27","doi-asserted-by":"publisher","DOI":"10.1126\/science.1188302"},{"key":"2026070601550942000_2026.07.01.735890v1.28","doi-asserted-by":"crossref","unstructured":"Ringquist, R. , et al., An immune-competent lung-on-a-chip for modelling the human severe influenza infection response. Nat Biomed Eng, 2025.","DOI":"10.1038\/s41551-025-01491-9"},{"key":"2026070601550942000_2026.07.01.735890v1.29","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.3697"},{"issue":"4","key":"2026070601550942000_2026.07.01.735890v1.30","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1016\/j.jcf.2021.10.004","article-title":"Modeling pulmonary cystic fibrosis in a human lung airway-on-a-chip","volume":"21","year":"2022","journal-title":"J Cyst Fibros"},{"key":"2026070601550942000_2026.07.01.735890v1.31","doi-asserted-by":"crossref","unstructured":"Ostedgaard, L.S. , et al., Lack of airway submucosal glands impairs respiratory host defenses. Elife, 2020. 9.","DOI":"10.7554\/eLife.59653"},{"key":"2026070601550942000_2026.07.01.735890v1.32","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbagen.2014.05.003"},{"issue":"2","key":"2026070601550942000_2026.07.01.735890v1.33","doi-asserted-by":"crossref","first-page":"5201","DOI":"10.1016\/j.actbio.2012.10.013","article-title":"Discovery of low mucus adhesion surfaces","volume":"9","year":"2013","journal-title":"Acta Biomater"},{"key":"2026070601550942000_2026.07.01.735890v1.34","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/j.ejpb.2018.06.029","article-title":"Surface modification with polyethylene glycol enhances colorectal distribution and retention of nanoparticles","volume":"130","year":"2018","journal-title":"Eur J Pharm Biopharm"},{"key":"2026070601550942000_2026.07.01.735890v1.35","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0608611104"},{"issue":"11","key":"2026070601550942000_2026.07.01.735890v1.36","doi-asserted-by":"crossref","first-page":"2597","DOI":"10.1002\/anie.201006849","article-title":"Biodegradable Nanoparticles Composed Entirely of Safe Materials that Rapidly Penetrate Human Mucus","volume":"50","year":"2011","journal-title":"Angewandte Chemie International Edition"},{"key":"2026070601550942000_2026.07.01.735890v1.37","doi-asserted-by":"publisher","DOI":"10.1038\/ncb2053"},{"issue":"11","key":"2026070601550942000_2026.07.01.735890v1.38","doi-asserted-by":"crossref","first-page":"2942","DOI":"10.1016\/j.bbamem.2015.09.009","article-title":"Mechanosensitive activation of CFTR by increased cell volume and hydrostatic pressure but not shear stress","volume":"1848","year":"2015","journal-title":"Biochim Biophys Acta"},{"key":"2026070601550942000_2026.07.01.735890v1.39","doi-asserted-by":"publisher","DOI":"10.1096\/fj.15-283002"},{"issue":"1","key":"2026070601550942000_2026.07.01.735890v1.40","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1186\/s40635-021-00374-y","article-title":"Rapid changes in mucociliary transport in the tracheal epithelium caused by unconditioned room air or nebulized hypertonic saline and mannitol are not determined by frequency of beating cilia","volume":"9","year":"2021","journal-title":"Intensive Care Med Exp"},{"key":"2026070601550942000_2026.07.01.735890v1.41","doi-asserted-by":"publisher","DOI":"10.1126\/science.1163600"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.64898\/2026.07.01.735890","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T08:55:31Z","timestamp":1783328131000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.64898\/2026.07.01.735890"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,2]]},"references-count":41,"URL":"https:\/\/doi.org\/10.64898\/2026.07.01.735890","relation":{},"subject":[],"published":{"date-parts":[[2026,7,2]]},"subtype":"preprint"}}