Multi-scale spatial heterogeneity enhances particle clearance in airway ciliary arrays

Mucus clearance constitutes the primary defence of the respiratory system against viruses, bacteria and environmental insults. This transport across the entire airway emerges from the integrated activity of thousands of multiciliated cells, each containing hundreds of cilia, which together must coordinate their spatial arrangement, alignment and motility. The mechanisms of fluid transport have been studied extensively at the level of an individual cilium, collectively moving metachronal waves and, more generally, the hydrodynamics of active matter. However, the connection between local cilia architecture and the topology of the flows they generate remains largely unexplored. Here, we image the mouse airway from subcellular (nm) to organ (mm) scales, characterizing quantitatively its ciliary arrangement and the generated flows. Locally, we measure heterogeneity in both cilia organization and flow structure, but, across the trachea, fluid transport is coherent. To examine this result, a hydrodynamic model was developed for a systematic exploration of different tissue architectures. Surprisingly, we find that disorder enhances particle clearance, whether it originates from fluctuations, heterogeneity in multiciliated cell arrangement or ciliary misalignment. This resembles elements of ‘stochastic resonance’, in the sense that noise can improve the function of the system. Taken together, our results shed light on how the microstructure of an active carpet determines its emergent dynamics. Furthermore, this work is also directly applicable to human airway pathologies, which are the third leading cause of deaths worldwide. Fluid flow through airways—necessary to keep lungs healthy and free from particles—occurs thanks to moving cilia. Here the authors show that defects in the arrangement of these cilia can facilitate particle clearance through the lungs.