An In Vitro Microfluidic Alveolus Model to Study Lung Biomechanics

The gas exchange units of the lung, the alveoli, are mechanically active and undergo cyclic deformation during breathing. The epithelial cells that line the alveoli contribute to lung function by reducing surface tension via surfactant secretion, which is highly influenced by the breathing-associated mechanical cues. These spatially heterogeneous mechanical cues have been linked to several physiological and pathophysiological states. Here, we describe the development of a microfluidically assisted lung cell culture model that incorporates heterogeneous cyclic stretching to mimic alveolar respiratory motions. Employing this device, we have examined the effects of respiratory biomechanics (associated with breathing-like movements) and strain heterogeneity on alveolar epithelial cell functions. Furthermore, we have assessed the potential application of this platform to model altered matrix compliance associated with lung pathogenesis and ventilator-induced lung injury. Lung microphysiological platforms incorporating human cells and dynamic biomechanics could serve as an important tool to delineate the role of alveolar micromechanics in physiological and pathological outcomes in the lung.

Automated summary

The gas exchange units of the lung, called alveoli, are mechanically active during breathing and undergo deformations. The epithelial cells lining the alveoli reduce surface tension through surfactant secretion, which is influenced by mechanical cues associated with breathing. These heterogeneous mechanical cues have been linked to various physiological and pathological states. In this study, a microfluidically assisted lung cell culture model was developed to mimic the respiratory motions of the alveoli. The effects of respiratory biomechanics and strain heterogeneity on alveolar epithelial cell functions were examined. Additionally, the potential application of this platform to model lung pathogenesis and ventilator-induced lung injury was assessed.