Abstract
Mucociliary clearance is a biomechanical mechanism of airway protection. It consists of the active transport along the bronchial tree of the mucus, a fluid propelled by the coordinated beating of a myriad of cilia on the epithelial surface of the respiratory tract. The physics of mucus transport is poorly understood because it involves complex phenomena such as long-range hydrodynamic interactions, active collective ciliary motion, and the complex rheology of mucus. We propose a quantitative physical analysis of the ciliary activity and mucus transport on a large panel of human bronchial cultures from control subjects, patients with asthma and chronic obstructive pulmonary disease obtained from endobronchial biopsies. Here we report on the existence of multiple ciliary domains with sizes ranging from the tens of a micron to the centimeter, where ciliary beats present a circular orientational order. These domains are associated with circular mucus flow patterns, whose size scales with the average cilia density. In these domains, we find that the radial increase of the ciliated cell density coupled with the increase in the orientational order of ciliary beats result in a net local force proportional to the mucus velocity. We propose a phenomenological physical model that supports our results.
Highlights
The continuous increase of chronic respiratory diseases worldwide, such as severe asthma, chronic obstructive pulmonary disease (COPD) and cystic fibrosis, represent a major threat for the quality of life
We quantified the ciliary activity of air–liquid interface (ALI) cultures from control subjects, 7 patients with mild asthma, patients with severe asthma and 7 patients with COPD
These values are in agreement with those previously reported on ALI cultures[24,25], but lower than those observed in the trachea, wherein the percentage of ciliated cell is about 50%26. ν is not altered in mild asthma (ν = 0.142, non significant) but strongly decreases to 0.055 (p = 0.0032) and 0.0395 (p = 0.0168) in severe asthma and COPD respectively (Fig. 1B)
Summary
The continuous increase of chronic respiratory diseases worldwide, such as severe asthma, chronic obstructive pulmonary disease (COPD) and cystic fibrosis, represent a major threat for the quality of life. The bronchial epithelium is the first barrier to protect the respiratory tract via an innate mechanism called mucociliary clearance It consists in the active transport of a sticky fluid, the mucus, via a myriad of cilia along the epithelial surface of the airways. The associated ciliary activity was not investigated It has been recently investigated in the ventricular system of mice brain, where highly organized directional patterns of cilia modules were discovered, leading to spatiotemporal modulated complex flow patterns of the cerebrospinal fluid, including swirls[9]. We report on the existence of multiple ciliary domains, whose sizes ranges from tens of microns to centimeters, where ciliary beats present a circular orientational order These domains are associated with a circular mucus flow patterns, whose size scales with the average cilia density. We discuss our findings in the context of severe asthma and COPD
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