Structure-function relationships of mucociliary clearance in human airways

Mucociliary clearance (MCC) is a key mechanical defense mechanism of the human airways, and clearance failure is linked to major respiratory diseases. However, our understanding of MCC mainly stems from animal models, limiting crucial insights into human barrier function and in-vitro modeling of airway diseases. Our study (Fig. 1 and 2) fills this knowledge gap and(1) maps the luminal distribution of ciliated and secretory cell types along the proximo-distal axis of the rat and human airway epithelium, (2) identifies species-specific differences in cilia properties and MCC, and (3) elucidates quantitative structural parameters of airway epithelia that predict MCC. Our broad range of experimental approaches and physics-based modeling translate into generalizable parameters to quantitatively benchmark the human-relevancy of MCC in different in vitro airway models, and to characterize distinct disease states. Fig 1: Graphical Abstract erj;64/suppl_68/PA2654/F1 F1 F1 Fig 2: Key metrics for comparing MCC in human branching generation (BG) 0-6 and in vitro ALI epi cultures differentiated in different media. A, luminal cell type composition; B, Measured and modeled clearance distance per ciliary beat. erj;64/suppl_68/PA2654/F2 F2 F2