Structure and function relationships of mucociliary clearance in human and rat airways

Doris Roth, Ayşe Tuğçe Şahin, Feng Ling, Niels Tepho, Christiana N. Senger, Erik J. Quiroz, Ben A. Calvert, Anne M. Does, Tankut G. Güney, Sarah Glasl, Annemarie Schadewijk, Laura Schledorn, Ruth Olmer, Eva Kanso, Janna C. Nawroth () and Amy L. Ryan ()
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Doris Roth: Helmholtz Zentrum München
Ayşe Tuğçe Şahin: Helmholtz Zentrum München
Feng Ling: Helmholtz Zentrum München
Niels Tepho: Helmholtz Zentrum München
Christiana N. Senger: University of Southern California
Erik J. Quiroz: University of Southern California
Ben A. Calvert: University of Southern California
Anne M. Does: Leiden University Medical Center
Tankut G. Güney: Helmholtz Zentrum München
Sarah Glasl: Helmholtz Zentrum München
Annemarie Schadewijk: Leiden University Medical Center
Laura Schledorn: Hannover Medical School
Ruth Olmer: Hannover Medical School
Eva Kanso: University of Southern California
Janna C. Nawroth: Helmholtz Zentrum München
Amy L. Ryan: University of Southern California

Nature Communications, 2025, vol. 16, issue 1, 1-17

Abstract: Abstract Mucociliary clearance is a vital defense mechanism of the human airways, protecting against harmful particles and infections. When this process fails, it contributes to respiratory diseases like chronic obstructive pulmonary disease (COPD) and asthma. While advances in single-cell transcriptomics have revealed the complexity of airway composition, much of what we know about how airway structure impacts clearance relies on animal studies. This limits our ability to create accurate human-based models of airway diseases. Here we show that the airways in female rats and in humans exhibit species-specific differences in the distribution of ciliated and secretory cells as well as in ciliary beat, resulting in significantly higher clearance effectiveness in humans. We further reveal that standard lab-grown cultures exhibit lower clearance effectiveness compared to human airways, and we identify the underlying structural differences. By combining diverse experiments and physics-based modeling, we establish universal benchmarks to assess human airway function, interpret preclinical models, and better understand disease-specific impairments in mucociliary clearance.

Date: 2025
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DOI: 10.1038/s41467-025-57667-z

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