Effects of Elasticity and Geometry on Cellular Uptake of Nanoparticles

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Effects of elasticity and geometry on cellular uptake of nanoparticlesPI: Huajian Gao, Brown UniversityAbstractThe objective of this proposal is to investigate the effects of elasticity and geometry on cellular uptake of nanoparticles based on a number of theoretical and simulation techniques developed by the PI?s research group on endocytosis and cell mechanics. The proposed work will include development of theoretical models of receptor-mediated endocytosis, calculations of free energy and phase diagrams of cell-particle attachment, interaction between elastic particles and cell membrane, cellular uptake of particles with large aspect ratios, as well as ultra-large scale coarse-grained molecular dynamics simulations of carbon nanotubes docking and wrapping into cell membranes via non-specific and specific interaction forces.Intellectual Merit:The proposed project complements existing multidisciplinary experimental research programs at Brown University on nanotoxicology in addressing the current lack of understanding on the roles of elasticity and aspect ratio of nanoparticles in the cellular uptake of carbon nanotubes and other potentially toxic nanoparticles. The proposed research will contribute to the fundamental understanding of mechanisms by which nanomaterials enter human and animal cells, an issue of tremendous societal concern regarding both beneficial and potential hazardous effects of nanotechnology which are projected to produce and release thousands of tons of nanomaterials into the environment in the coming decades. The project can also provide insights or guidelines for the development of efficient gene and drug targeting and delivery systems in biomedical technology. Broad impact:The proposed work at the interface between a number of traditional academic disciplines including mechanics, biology, biotechnology, nanotechnology, materials science, chemistry and physics will generate new knowledge and fundamental understanding that may provide insights and guidelines for a wide range of applications in nano- and bio-technologies. The educational components of the proposed research include training of a PhD student, development of two graduate courses in biomechanics, research experience and mentoring of students from under-represented groups and participation in the outreach programs to historically black colleges and K-12 in the Brown MRSEC program.