Two-dimensional materials consist of atomically thin layers with defined crystal structure and large lateral dimensions. This project focuses on two-dimensional transition metal dichalcogenides. These materials emerged in the past decade due to their unique optoelectronic properties, which are suitable for a wide range of applications in modern computing, biosensing, and communications, and the Internet of Things. Although these 2-dimensional materials have promise in affordable technologies, very little is known concerning their behavior at the interface with environmentally-relevant biological systems. This project will investigate the behavior of two-dimensional nanomaterials interacting with mammalian cells, focusing on three distinct aspects: the mechanism of cellular uptake; the potential structural transformations of the nanomaterial in the mammalian cells; and the reactivity in the cellular environment, especially to understand any potential inflammatory effects. The results of this project will be widely disseminated through peer-reviewed publications and conference presentations. Environmental stewardship is critical when using nanomaterials and the project will benefit society by providing data to guide regulation of new materials. Florida International University is a Hispanic Serving Institution with a very diverse student population and this project will engage students from underrepresented minority groups in science and engineering. Undergraduate and graduate students will be engaged in learning materials science and engineering, biology and environmental science, toward a convergent science and engineering education.The overarching goal of this project is to uncover fundamental modes of interaction between two-dimensional transition metal dichalcogenides that have potential applications for environmentally-relevant biological systems. Focusing on materials in their pristine form (non-functionalized) will facilitate assessment of the primary type of exposure expected during processing and handling of materials. Representative transition metal dichalcogenide materials applicable for future technologies were selected: molybdenum disulfide, a major component of electronic applications, and titanium disulfide, a potential photoacoustic therapeutic reagent. Skin exposure will be simulated by studying the materials interaction with Human Skin Fibroblast cells, and inhalation with A549 lung cancer cells. In addition, for these materials all of the known synthetic methods confer variable size and surface properties, intrinsic to the synthetic route, including ligands, defects, and adsorbed species. 2-dimensional transition metal dichalcogenides also exhibit polytypism which might be altered in the cellular environment. The investigator hypothesizes that the properties of the transition metal dichalcogenides are strongly correlated with certain phenomena: i). Physical interactions, involving the mechanism of cellular uptake; ii). In vitro phase transformations, referring to material phase changes in the cell; and iii). Chemical interactions, that could occur at the interface of the material with the cellular environment. The two selected materials, molybdenum disulfide and titanium disulfide, will be synthesized through all known 2-dimensional transition metal dichalcogenide synthetic methods and used in their pristine form to interact with lung cancer cells and skin cells, respectively. The project has the following objectives: establish the correlation between the synthetic method of the 2-dimensional transition metal dichalcogenide nanosheets and their cellular uptake in pristine form; elucidate the structural transformations of 2-dimensional transition metal dichalcogenide polytypes within the cellular environment by in situ Raman spectroscopy; and establish the correlation between 2-dimensional transition metal dichalcogenide properties and potential inflammatory effects in living cells. This project will contribute to a general understanding of the 2-dimensional transition metal dichalcogenide entry mechanism in the selected cells, the potential impacts of cellular environment on polytypes, and the potential inflammatory responses of exposed cells, as a function of nanosheet surface chemistry. Florida International University is a Hispanic Serving Institution with a very diverse student population and this project will engage students from underrepresented minority groups in science and engineering. Undergraduate and graduate students will be engaged in learning materials science and engineering, biology and environmental science, toward a convergent science and engineering education.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.