Spatiotemporal organization of cilia drives multiscale mucus swirls in model human bronchial epithelium

摘要

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.