Reveal the Effect of Mechanical Stretch on Virus‐Cell Membrane Fusion Based on a Microfluidic Chip

Lung-on-a-chip models are important for studying the onset and progression of respiratory diseases. However, existing lung chips often lack the ability to precisely regulate alveolar stretch deformation and rarely apply the 3D physiological microenvironment of alveoli to respiratory virus research. Here, we present a biomimetic 3D microfluidic chip microphysiological system for alveolar cells stretch visualization and investigate the effect of mechanical stretch on viral infection. We utilize a SARS-CoV-2 pseudovirus to infect alveolar epithelial cells cultured on the lung alveolus chip. Subsequently, we subjected the cells to varying degrees of mechanical stretch through membrane pressure deformation to examine the impact of these forces on viral invasion. Our study demonstrates that mechanical stretch can attenuate the fluorescence intensity of cytoskeletal proteins and regulate cytoskeletal protein rearrangements, which reduces cell membrane tension and thus virus-membrane fusion on the microfluidic chip for type II alveolar cells. The above features and results show that this chip has an extremely wide range of applications in cellular biomechanical testing, exploration of lung disease mechanisms, and clinical disease treatment.