Collaborative Research: Exploring self-organization of functional nucleic acid supramolecular assemblies with stimuli responsive properties

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This project is jointly funded by the Biomaterials program and the Established Program to Stimulate Competitive Research (EPSCoR)PART 1: NON-TECHNICAL SUMMARYThe study of ribonucleic acid or RNA is essential for understanding major cellular processes needed for life as well as the origin of various diseases. By using rationally designed RNAs as building blocks, it becomes possible to assemble Nucleic Acid NanoParticles, or NANPs, with pre-defined properties and architectures. The ability to readily respond to changes in biological environments makes biocompatible NANPs an attractive material for clinical use. Also, the biochemical versatility of NANPs can be combined with the optical, electronic, and magnetic properties of inorganic nanomaterials. These augmented NANPs can then be organized into supramolecular assemblies with controlled complexity and functions suitable for a broad range of biomedical, electronic, and imaging applications. However, despite the recent progress, it is still a challenge to engineer sophisticated, responsive, NANP supra-assemblies with regulated morphology. The proposed research program aims to develop a generalizable toolkit for the construction of stimuli-responsive NANP-based materials designed for end users in biotechnology. Building functional NANP supra-assemblies will improve the performance of current therapeutic systems, allow for the engineering of reconfigurable biomaterials, and become instrumental in furthering our understanding of the interactions governing the function of endogenous biomolecules. During this program, the undergraduate and graduate students will receive multidisciplinary training in experimental and computational RNA nanotechnology. This project will also expand the educational domain called ouRNAno that reaches out to and informs the community about recent advances in the field of RNA nanotechnology and will continue cultivating excitement for research through hosting community STEM events with local schools and science museum. PART 2: TECHNICAL SUMMARYRNA nanotechnology benefits from RNA’s ability to assemble through both canonical and non-canonical base pairings that form 12 geometric families. This offers a diverse set of structural and interacting motifs which allow for the construction of Nucleic Acid NanoParticles (NANPs). The versatile biochemistry of NANPs can be combined with the optical, electronic, and magnetic properties of inorganic nanomaterials. The further organization of these augmented NANPs into rationally designed supramolecular assemblies with controlled structural complexity can be used for application in biooptics, design of responsive devices, soft biomimetic machines, tissue mimics, and artificial muscles. Despite the existence of computational tools for NANP design, the use of NANPs as modular building blocks for supramolecular assemblies has never been systematically investigated. Therefore, this research program aims to address this gap in knowledge by developing a generalizable NANP-based programmable platform that simultaneously encodes targeted physicochemical, mechanical, and biological properties through networks of independently programmable architectural parameters. To achieve these goals, the team proposes three main objectives: (i) correlate the programmable parameters of NANPs with the physicochemical and mechanical properties of their supramolecular assemblies; (ii) evaluate the effect of functionalization of individual NANPs with inorganic nanomaterials on the physicochemical and mechanical properties of their supramolecular assemblies; and (iii) investigate the effect of stimuli-dependent kinetic pathways on the properties of functional supramolecular assemblies. This project will substantially advance the framework for the engineering of NANP supra-assemblies as novel stimuli-responsive materials and enable their use in a broad range of biomedical, electronic, and imaging applications.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.