Elucidating Multiparametric Nanoparticle - Intestinal Membrane Interactions in an In Vitro Model System

Trustees Of Boston University, Boston

Investigators

Abstract

Nanotechnology is the science and engineering discipline that utilizes the size-dependent properties of materials with dimensions of a few billionths of a meter to enhance their optical, electrical and chemical properties. The elementary building blocks of this discipline, engineered nanomaterials, are poised to find broad use in consumer products, but they have a potential for exposure to animals and humans. Since the interactions of nanomaterials with living organisms are insufficiently understood, there is a need for the development of appropriate assays that help to understand the interactions of engineered nanomaterials with living systems and identify potential risks. The main goals of this proposal are to implement an experimental model that improves the current knowledge of how ingested nanomaterials interact with the small intestine and to clarify what role general nanomaterial properties, such as size, shape and surface charge have in these interactions. The knowledge obtained in this project will eventually help minimize the possible adverse health impacts of ingested nanoparticles. In addition to its scientific mission, the project also has clear education and outreach components. The project forms the basis for at least one PhD thesis in the area of nanotechnology. Furthermore, workshops and seminars will be developed that introduce college and high school students as well as interested teachers to the subject matter of the proposal. The course material will be disseminated through the world-wide-web and educate the public about nanotechnology in consumer products and provide a scientific basis for the evaluation of potential health risks. The ultrafine size of nanoparticles is associated with a large surface-to-volume ratio, which could lead to toxic interactions with cellular systems. Although it is accepted that interactions between human intestinal cells and engineered nanomaterials depend on multiple material properties, it is still not clear if and how individual material properties synergistically enhance their cytotoxic effects. This proposal will address this important question on two levels of investigation. A systematic screening of membrane damage and transmembrane transport for an extended library of well characterized gold nanoparticles, will make it possible to correlate nanoparticle morphology, size and surface charge with adverse effects on the intestinal membrane. In a second step, novel imaging methods, such as plasmon coupling microscopy, will be applied to monitor and image nanoparticle-cell interactions, intracellular nanoparticle distributions, and nanoparticle transmembrane transport. Electromagnetic interactions between the gold nanoparticles make it possible to not only track individual nanoparticles in the intestinal membrane, but also to monitor their association into larger units as function of location and time. This gain in information content, when combined with conventional fluorescence microscopy, will elucidate the mechanisms underlying the interactions between nanoparticles and the intestinal membrane for characteristic nanoparticle size, shape, and surface charge combinations. Overall, the proposed experiments will provide the quantitative foundation for developing accurate computational models for evaluating the effects of nanoparticles on intestinal membranes. 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.