CAREER: Multi-stimuli Responsive DNA-Nanoshells - Compartmentalizing Molecules at the Nanoscale for Enhanced Reaction Selectivity and Sensitivity

University Of Connecticut, Storrs CT

Investigators

Abstract

Viruses have evolved self-destruct mechanisms that allow them to release their contents when they are inside the right host. The viruses are decorated with molecules that trigger their degradation when they encounter specific enzymes found within certain biological systems. Using inspiration from how virus particles respond to their environment in highly specific ways, the research group of Professor Jessica Rouge at the University of Connecticut is developing new chemical strategies to synthesize shells of very small size that can both controllably encapsulate small molecules and release them in response to specific stimuli in complex mixtures. Such strategies are important for developing more sensitive biological sensors and more accurate drug delivery systems. This project provides graduate and undergraduate students multidisciplinary research training in nanoscience, chemical synthesis, and biochemistry. In addition, an initiative entitled "Catalyzing Curie-osity" is launched to engage high school teachers and students throughout the state of Connecticut. Through this joint initiative with the UConn Early College Experience program, affordable lab protocols are being designed focusing on the fundamental tools and techniques of bio-nanoscience. These lab modules will be individually tailored to the needs and resources of specific high schools, giving students hands -n experience with this exciting class of nanomaterials and preparing them for future careers related to nanotechnology and chemistry. With the support of the Macromolecular, Supramolecular and Nanochemistry program, the Rouge Group is developing novel chemical crosslinking strategies that can be incorporated into DNA nanomaterials for controlling their assembly and disassembly in complex biological environments. Using a novel DNA-surfactant assembly strategy that generates DNA nanoshells compatible with cells and enzymes, the major goal of this work is to synthesize a combination of peptide and synthetic crosslinkages that can maintain the nanomaterials stability in biological systems while exhibiting selectivity for certain chemical and biochemical stimuli. These stimuli, including temperature and pH changes, or exposure to specific enzyme classes, will be used to gate the release of small molecules for initiating chemical and/or biochemical reactions. Through this work the following goals are addressed: 1) the design of a library of thermoresponsive crosslinkers that enables remotely controlled substrate release, 2) the design of ligand-cargo communication schemes for sensing the local environment of the DNA-nanoshells, and 3) control over solution reaction selectivity via stepwise substrate release from multi-layered peptide crosslinked DNA-nanoshells. Compartmentalization of different substrates within the DNA-nanoshell layers will allow the team to study release rates and subsequent reaction rates of diverse molecules in aqueous systems. 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.