RT Journal Article
SR Electronic
T1 Breathing on Chip: Biomechanical forces change airway epithelial cell biology in a human Airway Lung-Chip
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.05.07.443164
DO 10.1101/2021.05.07.443164
A1 Janna C. Nawroth
A1 Doris Roth
A1 Annemarie van Schadewijk
A1 Abilash Ravi
A1 Tengku Ibrahim Maulana
A1 Christiana N. Senger
A1 Sander van Riet
A1 Dennis K. Ninaber
A1 Amy L Ryan
A1 Pieter S. Hiemstra
A1 Anne M. van der Does
YR 2021
UL http://biorxiv.org/content/early/2021/05/08/2021.05.07.443164.1.abstract
AB Human lung function is intricately linked to the mechanics of breathing; however, it remains unknown whether and how these mechanical cues shape human lung cellular biology. While respiration-related strains and fluid flows have been suggested to promote alveolar epithelial cell function, the study of such fundamental mechanisms in the conducting airway epithelium has been hindered by the lack of suitable in vitro airway models. Here, we developed a model of human bronchial airway epithelium using well-differentiated primary cell cultures on a commercial Organs-on-Chips platform that enables the application of breathing-associated airflow and cyclic strain. It furthermore features optional endothelial cell co-culture to allow for crosstalk with the vascular compartment. Using this model, we evaluated the impact of airflow and physiological levels of cyclic strain on airway epithelial cell differentiation and function. Our findings suggest that breathing-associated mechanical stimulation changes epithelial composition, reduces secretion of IL-8, and downregulates gene expression of matrix metalloproteinase 9, fibronectin, and other extracellular matrix (ECM) factors. These results indicate that breathing-associated forces are important modulators of airway epithelial cell biology and that their fine-tuned application could generate models of specific epithelial phenotypes and pathologies.Competing Interest StatementThe authors have declared no competing interest.