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Particle size determines mucociliary transport mechanisms in normal and cystic fibrosis airways
Preprint   Open access

Particle size determines mucociliary transport mechanisms in normal and cystic fibrosis airways

Michael Scott, Kaleb C Bierstedt, Weijie Du, Mitchell J Riley, Anthony J Fischer and Yuliang Xie
bioRxiv
07/02/2026
DOI: 10.64898/2026.07.01.735890
PMID: 42427561
url
https://doi.org/10.64898/2026.07.01.735890View
Preprint (Author's original) This preprint has not been evaluated by subject experts through peer review. Preprints may undergo extensive changes and/or become peer-reviewed journal articles. Open Access

Abstract

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 ( e.g., 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 µm polystyrene particles clear rapidly, whereas 102 µm 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.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 ( e.g., 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 µm polystyrene particles clear rapidly, whereas 102 µm 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.

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