Disentangling mucus rheology and transport efficiency in human airways

Abstract 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.