Mechanical strain mimicking breathing amplifies alterations in gene expression induced by SiO₂ NPs in lung epithelial cells

Abstract

The effects of engineered nanomaterials on human health are still intensively studied in order to facilitate their safe application. However, relatively little is known how mechanical strain as induced in alveolar epithelial cells by breathing movements modifies biological responses to nanoparticles (NPs). In this study, A549 cells as a model for alveolar epithelial cells were exposed to 25 nm amorphous colloidal silica NPs under dynamic and static culture conditions. Gene array data, qPCR, and ELISA revealed an amplified effect of NPs when cells were mechanically stretched in order to model the physiological mechanical deformation during breathing. In contrast, treatment of cells with either strain or NPs alone only led to minor changes in gene expression or interleukin-8 (IL-8) secretion. Confocal microscopy revealed that stretching does not lead to an increased internalization of NPs, indicating that elevated intracellular NP accumulation is not responsible for the observed effect. Gene expression alterations induced by combined exposure to NPs and mechanical strain showed a high similarity to those known to be induced by TNF-α. This study suggests that the inclusion of mechanical strain into in vitro models of the human lung may have a strong influence on the test results.

Keywords:

• Silica nanoparticles
• A549 cells
• mechanical strain
• gene expression
• inflammation

Acknowledgements

The authors thank Eduard Arzt for continuing support of their work at INM. The authors also thank Anika Schwarz and Anja Colbus for particle characterization, Silke Kiefer for RNA isolation and Marcus Koch for electron microscopy analysis of the NPs.

Declaration statement

The authors report no conflict of interest.

Additional information

Funding

This study was conducted in frame of the Leibniz Research Alliance Nanosafety and was partially supported by the Leibniz-Association.