Active mucus–cilia hydrodynamic coupling drives self-organization of human bronchial epithelium
In our lungs, billions of cilia line the walls and beat in an organized way to clear mucus from our bronchi, since the first day of our lives. This mechanism is called mucociliary clearance. Together with our collaborators, we have pooled our expertise in experimental physics, fluid mechanics, developmental biology and pneumology to unlock its secrets.
We now have a better understanding of the unique ability of these millions of cilia to collectively organize their beating directions with the common goal of propelling mucus over long distances. Our work could prove decisive in the search for a treatment for chronic respiratory diseases (severe asthma or chronic obstructive pulmonary disease) that affect hundreds of millions of people. We have established that it is the biophysical interactions between microscopic cilia beating and centimeter-scale mucus displacement that govern the dynamic orientation of ciliary beats. We show that the ciliary beats align in the presence of mucus and misalign when the mucus is removed and reveal, through modeling, that the flow force exerted by the mucus on the cilia aligns their beating direction, thus allowing for efficient transport of mucus along the bronchi and trachea. To show this, we have reconstructed a bronchial epithelium in-vitro, consisting of ciliated cells and mucus-producing cells, from human cells taken by bronchoscopy, allowing us to measure both mucus transport and ciliary beats.
We have developed a computational fluid mechanics model to capture and predict the coupling between the spatial organization of vibrating cilia and the hydrodynamics of mucus exhibiting different organizational flow regimes. We have biologically characterized the planar polarization of ciliated cells allowing us to build up true maps of ciliary beat orientation over the whole tissue.
Ref : Nature Physics, Nature Publishing Group, 2020, (10.1038/s41567-020-0980-z). (hal-02914172)