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Structure-function relationships of mucociliary clearance in human airways
Preprint   Open access

Structure-function relationships of mucociliary clearance in human airways

Doris Roth, Ayşe Tuğçe Şahin, Feng Ling, Christiana N Senger, Erik J Quiroz, Ben A Calvert, Anne van der Does, Tankut G Güney, Niels Tepho, Sarah Glasl, …
bioRxiv : the preprint server for biology
Cold Spring Harbor laboratory
12/26/2023
DOI: 10.1101/2023.12.24.572054
PMCID: PMC10769450
PMID: 38187619
url
https://doi.org/10.1101/2023.12.24.572054 View
Preprint (Author's original)This preprint has not been evaluated by subject experts through peer review. Preprints may undergo extensive changes and/or become peer-reviewed journal articles. Open Access

Abstract

Mucociliary clearance (MCC) is a key mechanical defense mechanism of the human airways, and MCC failure is linked to major respiratory diseases. While single-cell transcriptomics have unveiled the cellular complexity of the human airway epithelium, our insights into the mechanical structure-function relationships that drive MCC mainly stem from animal models, limiting our understanding and modeling of human airway barrier function and disease. This study addresses these knowledge gaps and (1) reveals key differences in abundance and proportion of ciliated and secretory cell types at the luminal surface along the proximo-distal axis of the human and rat airway epithelium, (2) identifies ciliary beat properties that vary between species, and (3) quantitatively links these structural differences to differences in particle clearance function using a combination of experimental approaches and physics-based modeling. Finally, we leverage these structure-function relationships to develop metrics of organotypic tissue composition and clearance function in human airway epithelia, leading to the establishment of human-specific benchmarks for respiratory cultures, and allowing us to quantitatively compare the mucociliary machinery of different model systems, culture conditions, and disease states.

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