Molecular Mechanisms Underlying Nanomaterial Toxicity or Biocompatibility
EMSL Project ID
49059
Abstract
This proposal covers research conducted with funding from several agencies, including NIEHS and the NSF-funded Center for Sustainable Nanotechnology. The rapid growth in nanotechnology is expected to increase human exposure to nanomaterial, including certain forms of cerium oxide (ceria) nanoparticles (NPs) used as catalysts in automotive exhaust systems among many other applications. When inhaled, NPs have been shown to reach the alveolar region and induce adverse effects, but the underlying mechanisms are far from being understood. Harmful effects of NPs have been attributed to unique properties of material at the nano-scale, such as a large surface-area-to-mass ratio leading to increased reactivity and potentially cellular damage. However, the majority of in vitro studies characterizing the impact of NPs on cells that line the respiratory tract have been conducted in cells exposed to NPs in growth media, introducing NP properties and processes that are irrelevant to inhaled NP exposure in vivo. These include the formation of large NP agglomerates or coronas of growth media proteins at the NP surface, among other processes. Large agglomerates might no longer carry the properties of the individual NP and are easily recognized by the alveolar macrophages, but dispersed NPs have been shown to escape phagocytosis and translocate across the alveolar wall into the pleura and the circulatory system. Similarly, coronas formed in growth media are different than those formed in the lung-lining fluid and are likely to engage different cellular interactions and response. To mimic in vivo exposure to airborne NPs, we established the exposure of alveolar cells to aerosolized NPs at the air-liquid interface (ALI), including a quartz crystal microbalance for accurate measurements of the actual cellular dose. Using this approach and building on our experience in fluorescence imaging with single molecule sensitivity and molecular biology techniques, we will delineate realistic relationships between properties of individual airborne NPs or nanoscale aggregates and their cellular interactions, fate and response. Ultimately, our work will provide new understanding and predictive evaluations of responses to nanoparticle exposure. This information will guide the design of safer nanomaterials.
Project Details
Start Date
2015-10-01
End Date
2016-09-30
Status
Closed
Released Data Link
Team
Principal Investigator
Team Members
Related Publications
Mitchell HD, LM Markillie, WB Chrisler, MJ Gaffrey, D Hu, CJ Szymanski, Y Xie, ES Melby, A Dohnalkova, RC Taylor, EK Grate, SK Cooley, JE McDermott, A Heredia-Langner, and G Orr. 2016. "Cells Respond to Distinct Nanoparticle Properties with Multiple Strategies as Revealed by Single-Cell RNA-Seq." ACS Nano 10(11):10173-10185. doi:10.1021/acsnano.6b05452