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

Abstract

Mucus clearance constitutes the primary defence of the respiratory system against viruses, bacteria and environmental insults [1]. 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 [2,3]. The mechanisms of fluid transport have been studied extensively at the level of an individual cilium [4,5], collectively moving metachronal waves [6-10], and more generally the hydrodynamics of active matter [11,12]. 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 the sub-cellular (nm) to the organ scales (mm), characterising quantitatively its ciliary arrangement and the generated flows. Locally we measure heterogeneity in both cilia organisation 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' [13][14][15] in a self-assembled biological system. Taken together, our results shed light on how the microstructure of an active carpet [16,17] determines its emergent dynamics. Furthermore, this work is also directly applicable to human airway pathologies [1], which are the third leading cause of deaths worldwide [18].

Fluid mechanics of mosaic ciliated tissues

“…Extra endogenous loadsγ e < 0, as expected for internal tissues, appear as an additional contribution to the ambient floẇ γ a +γ e . These loads will contribute to (5) as lower values of λ, and indeed, consistently larger, yet still low coverage fractions of the airways of several animals have been estimated to be 0.4 − 0.5 [14], qualitatively consistent with Fig. 4.…”

A Quantitative Interspecies Comparison of The Respiratory Mucociliary Clearance Mechanism

“…This would explain, why our attempt to establish a generally valid model for the interrelationship of the metachronal wave properties and the mucociliary transport was not successful. Besides the rheological conditions [11,70], the geometrical conditions, such as the ciliary spacing [12,71], the ciliary orientation [72], the proportion and the distribution of ciliated cells [73,74], but also the depth of the mucus and the periciliary layer [71], are known to also determine mucociliary transport, which, in turn, is contemporary seen to interact and to coemerge with those rheological and geometrical conditions during the morphogenesis of the system under study.…”

Extremely Broadband Stochastic Resonance of Light and Enhanced Energy Harvesting Enabled by Memory Effects in the Nonlinear Response

“…This exciting prediction, with potentially far-reaching technological implications, awaits experimental confirmation. Beyond single-resonator physics, our Letter paves the way for studying various noise-assisted processes (e.g., noise-assisted transport [63][64][65][66]) in nonlinear and non-Markovian cavity arrays. Such arrays could be used to explore how memory effects can render complex networks resilient against breakdown of synchronization [67].…”