Spatial organization of cilia tufts governs airways mucus transport: Application to severe asthma

We study the coupling between both density and spatial repartition of beating cilia tufts, and the coordinated transport of mucus in an \textit{in-vitro} epithelial model. We use a fully differentiated model epithelium in air liquid interface (ALI) obtained from endo-bronchial biopsies from healthy subjects and patients with asthma. The asthma phenotype is known to persist in the model. Mucus transport is characterized by the trajectories and velocities of microscopic beads incorporated in the mucus layer. When the beating cilia tufts density is higher than $d_{c}=$11/100x100 $\mu$m$^2$ a spherical spiral coordinated mucus transport is observed over the whole ALI chamber (radius$=$6mm). Below $d_{c}$, local mucus coordinated transport is observed on small circular domains on the epithelium surface. We reveal that the radii of these domains scale with the beating cilia tufts density with a power 3.7. Surprisingly, this power law is independent on cilia beat frequency, concentration and rheological properties of mucus for healthy subject and patient with asthma. The rotating or linear mucus transport is related to dispersion of the cilia tufts on the epithelium surface. We show that impaired mucus transport observed in severe asthma model epithelia is due to a drastic lack and dysfunction of cilia tufts.