CAREER: Nucleic Acid-Peptide-Mineral Hybrid Assemblies and Nano-Devices

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NON-TECHNICAL SUMMARYLife at various scales can be viewed as a dynamic self-assembling system. Living organisms have developed their unique strategies to build soft and hard tissues and the resulting hybrid materials have excellent properties that remain far beyond those of their artificial counterparts. To engineer nature-inspired self-assembled molecular systems and functional materials, which can communicate with cells and regulate biological events, is one of the grand goals that is highly relevant to scientific areas ranging from synthetic biology, nanotechnology, regenerative medicine, to materials science. This project aims to develop self-assembling Nucleic Acid-Peptide-Mineral (NAPM) hybrid molecular tiles as building blocks to create robust, programmable, smart, and functional biomaterials and nanodevices. The unique structural programmability of DNA will be integrated with the advantageous mechanical properties and functionality of minerals, peptides, and RNA to diversify and enhance the chemical and physical functionality of DNA nanostructures. This new platform will expand the programmable assembly in DNA nanotechnology from the nanometer scale to microns, furnish knowledge on the self-assembly of novel hybrid tiles, and lead to the discovery of new functionalities associated with these hybrid systems. In addition, this project integrates research with graduate and undergraduate education and introduces innovative programs for high schools, K-12 students, and community-wide outreach.TECHNICAL SUMMARYThe overarching goal of this project is to develop a hybrid molecular tile system employing minerals and peptides that are integrated into programmable DNA nanostructures to generate new self-assembling hybrid materials. The main scientific challenges to address are: (1) how to develop a general method to rigidify DNA nanostructures while maintaining the programmability of DNA, (2) how to create the surface preference for controllable precise deposition of different types of minerals, (3) what are the self-assembly behaviors of these new hybrid tiles and how to guide their assembly to create novel structures at micron scales, and (4) how to achieve dynamic responsive reconfiguration in this new system. In this project, these challenges will be tackled by developing structurally strengthening deposition methods of minerals employing regulating peptides and RNA molecules to produce NAPM hybrid tiles; developing geometric matching and molecular programming rules for the hybrid tiles to direct their self-assembly; and engineering novel reconfiguration mechanisms by integrating switchable nucleic acid structures to reversibly change the size, shape, and surface chemistry of the hybrid materials responding to external stimuli. This project will finally create hybrid materials that inherit the programmability of DNA and RNA while displaying enhanced mechanical properties. It will also develop a toolkit for integrating the physicochemical and mechanical properties of inorganic materials with biological materials.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.