Tying Distinct Nanoparticle Properties to Cell Surface Interactions and Intracellular Fate
EMSL Project ID
40093
Abstract
The increasing use of engineered nanomaterials in industrial and medical applications is expected to increase both unintended environmental or occupational exposures and intended medical or direct consumer exposures, but the impact of such exposures on human health is unclear. The potential toxicity or biocompatibility of engineered nanomaterials is governed by the cellular interactions and fate of the particles, which dictate the cellular response and ultimately determine the impact on human health. The cellular interactions and subsequent response of the cells are governed by the physical and chemical properties of the particles, but the relationships between particle properties and these cellular processes are far from being understood. Furthermore, the properties of nanomaterials are likely to be modified by the environment, such as ambient air, but these changes are also unclear. The purpose of this proposal is to identify relationships between distinct properties of airborne engineered nanomaterials and their cell surface interactions and intracellular fate in alveolar epithelial cells at the air-liquid interface with the goal of supporting predictive evaluation of inhaled nonmaterial's toxicity or biocompatibility. Airborne nanomaterials that enter the respiratory tract are likely to be deposited in the alveolar region, where alveolar epithelial cells are found. These cells provide a vulnerable target for particles that escape the first line of defense by the alveolar macrophages. Accumulating observations indicate that nanomaterials are likely to be presented to alveolar cells in vivo as individual particles or small nanoscale aggregates, which differ from the larger particles in their ability to interact with the cells. We will establish methods for realistic exposures to well-defined monodispersed nanomaterials in ambient air for delineating relationships between distinct properties that are relevant to airborne particles and their impact on alveolar epithelial cells at the air-liquid interface. Size exclusion methods will ensure exposures to individual nanoparticles or small nanoscale aggregates, as they are likely to be presented to the cells in vivo. Using EMSL unique capabilities in quantitative fluorescence imaging with single molecule sensitivity, combined with molecular biology techniques, we will investigate the cellular interactions and fate of one nanoparticle or nanoscale aggregate at a time, delineating cellular processes that are relevant to the properties of the individual nanoparticle and the exposures in vivo. Furthermore, EMSL diverse capabilities in molecular and atomic level investigations of materials will be used to determine the physical and chemical properties of the nanoparticles at the air-liquid interface and inside the cell. This approach will derive changes that might occur to nanomaterials in the ambient air or in the cellular environments and identify properties that truly impact the cells in vivo. Together, our studies will gain critical new relationships between properties of airborne nanomaterials and their cellular interactions, fate and response, supporting predictive evaluations of toxicity or biocompatibility of inhaled nanomaterials. The new information will have a large scale impact by guiding preventative approaches and the design of safer nanomaterials for new industrial and medical applications.
Project Details
Project type
Large-Scale EMSL Research
Start Date
2010-10-01
End Date
2013-09-30
Status
Closed
Released Data Link
Team
Principal Investigator
Team Members
Related Publications
Hinderliter PM, KR Minard, G Orr, WB Chrisler, BD Thrall, JG Pounds, and JG Teeguarden. 2010. "ISDD: A Computational Model of Particle Sedimentation, Diffusion and Target Cell Dosimetry for In Vitro Toxicity Studies." Particle and Fibre Toxicology 7(November):Article No. 36. doi:10.1186/1743-8977-7-36
Karakoti AS, P Munusamy, KE Hostetler, VK Kodali, SVNT Kuchibhatla, G Orr, JG Pounds, JG Teeguarden, BD Thrall, and DR Baer. 2012. "Preparation and Characterization Challenges to Understanding Environmental and Biological Impacts of Nanoparticles." Surface and Interface Analysis 44(8):881-889. doi:10.1002/sia.5006
Orr G, WB Chrisler, KJ Cassens, R Tan, BJ Tarasevich, LM Markillie, RC Zangar, and BD Thrall. 2011. "Cellular Recognition and Trafficking of Amorphous Silica Nanoparticles by Macrophage Scavenger Receptor A." Nanotoxicology 5(3):296-311. doi:10.3109/17435390.2010.513836
Xie Y, NG Williams, A Tolic, WB Chrisler, JG Teeguarden, BL Maddux, JG Pounds, A Laskin, and G Orr. 2012. "Aerosolized ZnO nanoparticles induce toxicity in alveolar type II epithelial cells at the air-liquid interface." Toxicological Sciences 125(2):450-461. doi:10.1093/toxsci/kfr251
Zhang H, KE Burnum, ML Luna, BO Petritis, JS Kim, W Qian, RJ Moore, A Heredia-Langner, BJM Webb-Robertson, BD Thrall, DG Camp, II, RD Smith, JG Pounds, and T Liu. 2011. "Quantitative proteomics analysis of adsorbed plasma proteins classifies nanoparticles with different surface properties and size." Proteomics 11(23):4569-4577. doi:10.1002/pmic.201100037