Impact of physiological strain on lung epithelial cells by exposure to aerosolised quartz silica in a perfused bioreactor

Understanding how inhaled particles that can reach the deep lung induce adverse effects requires in vitro platforms that reflect key exposure and mechanical features of the alveolar environment. Here, we engineered a dynamic air–liquid interface bioreactor integrating physiological cyclic strain, basal perfusion, and apical aerosol delivery. Cyclic breathing-like deformation of an elastic membrane is driven by pressure-regulated airflow, while real-time aerosol deposition is quantified using an integrated quartz crystal microbalance, enabling precise control of delivered dose. Human alveolar epithelial cells (A549) cultured under breathing-like conditions exhibited moderate, adaptive changes in morphology, cell density, and gene expression, indicative of a low-stress mechanoadaptive state. Using this platform, cells were exposed to aerosolised crystalline quartz (DQ 12 ) at a sub-cytotoxic dose, representative of occupational exposure. Particle deposition under dynamic conditions induced distinct transcriptional shifts in A549 cells, particularly in inflammatory and adhesion-related genes, without triggering broader stress or mucin-associated responses. Together, these results demonstrate how coupling physiologically-relevant mechanical actuation with quantitative aerosol exposure provides a robust physiological platform for investigating particle–lung epithelial interactions under realistic human exposure scenarios.