Method Development for Quantification of Physicochemical Properties of Engineered Nanoparticles and Their Local-Scale Biological Effects

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1235166ChenThis NSF award supports work to investigate the impacts of engineered nanomaterials on local scale surface physicochemical properties of cells. It is important to the general public by providing the fundamental knowledge about the toxic impacts of nanomaterials at nanometer scale and help understand and differentiate risks of bulk or aggregated and nanoscale materials. Intellectual Merit: Many traditional toxicological experiments on nanomaterials have not ended up with real nano-sized materials in aqueous media, largely because most nanomaterials are subject to slow or fast aggregation in the testing systems. The observed toxicity and related mechanisms are likely associated with the properties of aggregated clusters and their enlarged sizes. However, un-aggregated nanoscale engineered nanoparticles (NPs) and their local interactions with heterogeneous cell surfaces influence their subsequent toxic effects, which are not well documented yet. Thus, the toxicity mechanisms of engineered NPs are not clear yet. Our hypothesis to be tested is that local interactions between single NPs and cells inevitably result in changes in the physicochemical properties of cells at nanoscale. To perform quantitative measurements of heterogeneous surface properties of cells with and without exposure to NPs, we will develop novel experimental methods with the unique advantages of atomic force microscopy (AFM). The project objectives include the quantification of: 1) biomechanical (i.e., hardness and elasticity) properties of microbial cells at local-scale, which affect cellular integrity, flexibility, and motility; 2) adhesiveness, which influences cell adhesion to environmental surfaces; 3) hydrophobicity, which affects the interfacial energy and surface interactions; and 4) local surface electrostatic potential, which influences the stability of cell systems and interaction energy. Moreover, at the genetic level, we will also study NP-DNA interactions via imaging in liquid to show the dynamic binding between NPs and DNA, structural conformational changes in DNA upon exposure to NPs, and DNA transcription under the potential influence of NP binding. Broader Impacts: If successful, the proposed research will establish AFM-based scanning probe approaches that can quantify the local-scale surface physicochemical properties during the interactions between NPs and biological systems (cells and DNA molecules) and provide a unique angle for exploring the toxic effects of engineered nanomaterials. It will fill a data gap in the impacts of local scale NP interactions and improve our fundamental knowledge in toxicity of engineered nanomaterials. These findings will ultimately produce broader impacts on industrial manufacturers, regulatory authorities, and researchers for sustainable nanomaterial design, regulation formulation, and eco-responsible management in use, handling, and disposal. In addition, we will establish synergies between the project research and college education by motivating undergraduates and graduates in STEM research areas, and navigating them to the frontiers of nanoscience and nanotechnology. The PIs will provide funding to get underrepresented undergraduate researchers involved in the research project.