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Biology subjects

Briole, A.

Publications and source records attributed to Briole, A..

2 recordsLinked to original sources

Disentangling mucus rheology and transport efficiency in human airways

The protection of the respiratory tract relies on a layer of mucus that is transported along the epithelial surface by the beating of millions of microscopic cilia. This mechanism, called mucociliary clearance, is defective in chronic respiratory diseases. Since these pathologies alter mucus rheology, mucus transport efficiency is hypothesized to rely on its mechanical properties. Yet, this link is difficult to test due to limited experimental models. Here, we introduce an experimental framework that enables us to identify conditions associated with efficient mucus transport or arrest. Strikingly, we show that cilia are able to efficiently propel mucus with properties ranging from a viscoelastic fluid to an elastic solid, revealing that bulk mucus rheology is not the critical determinant of clearance failure. Instead, we demonstrate that the efficiency of mucociliary clearance is governed by the hydration of a thin fluid layer at the cilia-mucus interface. Finally, we use a hydrodynamic model informed by measurements on ciliary beat patterns to infer the properties of this critical layer under both transported and arrested mucus conditions. This work not only offers a novel understanding of the fundamental physical mechanism of mucus transport, but also provides a well-defined and quantitative assay to test effects of mucolytic agents or drugs on mucus clearance.

biophysics↗

Robust ciliary flows protect early Xenopus embryos from pathogens independent of multiciliated cell patterning

During the early stages of development, the skin of the Xenopus embryo is covered by around two thousand evenly distributed multiciliated cells (MCCs). This striking spatial distribution is believed to maximise the generation of superficial flows at the scale of the embryo. However, the specific role of regular MCC distribution and the physiological function of vigorous ciliary activity remain elusive. We investigate the extent to which superficial flows provide protection against external pathogens before the immune system matures, by combining experimental and computational approaches. First, we cultivated epithelial explants in order to quantify the distribution of MCCs, beating frequencies, and three-dimensional fluid flows. We then use these data to validate a computational fluid dynamics model. Using this model, seeded with structural data from whole embryos, our simulations reveal that the collective ciliary beatings create a robust liquid shield along the embryonic flank, which is highly effective at clearing pathogens from the vicinity of the epithelial surface. Through parametric analyses, we further demonstrate that this protective function is remarkably resilient. Indeed, the effectiveness of pathogen clearance is primarily governed by the overall characteristic velocity of the cilia and is less affected by moderate variations in MCC density and spatial organisation. Our findings suggest that, rather than optimising energy consumption, the biological system prioritises functional robustness to ensure reliable protection.

biophysics↗