Contractility of Airway Smooth Muscle Cell in Response to Zinc Oxide Nanoparticles by Traction Force Microscopy

Zinc oxide nanoparticles (ZnO-NPs) have been widely used in engineering and biomedicine. However, their adverse pathological effects and mechanisms, especially the biomechanical effects on respiratory system where airway smooth muscle cell (ASMC) contractility regulates the airway response and lung function, are not fully understood. Herein, we used traction force microscopy (TFM) method to investigate whether ZnO-NPs of different concentrations (0.1-10 μg/mL) can alter ASMC contractility (basal and agonist-stimulated) after a short-term exposure and the potential mechanisms. We found that ZnO-NPs exposure led to a decrease of ASMC viability in a dose-dependent manner. Notably, basal contractility was enhanced when the concentration of ZnO-NPs was less than 0.1 μg/mL and decreased afterwards, while KCl-stimulated contractility was reduced in all cases of ZnO-NPs treated groups. Cytoskeleton structure was also found to be significantly altered in ASMC with the stimulation of ZnO-NPs. More importantly, it seems that ZnO-NPs with low concentration (< 0.1 μg/mL) would change ASMC contractility without any apparent cytotoxicity through disruption of the microtubule assembly. Moreover, our results also emerged that ASMC contractility responses were regulated by clathrin-mediated endocytosis and cytoskeleton remodeling. Together, these findings indicate the susceptibility of cell mechanics to NPs exposure, suggesting that cell mechanical testing will contribute to uncover the pathological mechanisms of NPs in respiratory diseases.