Responsive materials from self-assembling nucleic acid nanoshapes

NON-TECHNICAL SUMMARY

Nucleic acids are biomolecules that lend themselves for the construction of new composite materials because of their ability to self-assemble in a predetermined fashion and to bind various other non-nucleic acid components. The Hermann lab will design and develop new materials from modules composed of the two principal nucleic acid types, RNA and DNA, which in addition contain chemically diverse ligands that serve as permanent components, for example, to endow the materials with stimulus-responsive functionality, or as transient trigger to control material assembly and dissociation.

The new composite nanomaterials will allow the controlled spatial arrangement of these ligands in regular patterns at nanometer distances. For the preparation of such nucleic acid materials, the Hermann lab will develop procedures that apply successive addition and selective removal (“subtraction”) of nucleic acid components by exploiting the distinct chemical reactivity of the RNA and DNA components.

The materials created under this research have potential applications in the creation of functional surface patterns at the nanometer scale for the fabrication of sensor surfaces for the real-time detection of environmental stimuli and toxins, recognition of biomedical analytes in healthcare applications, templates for semiconductor fabrication, and surface coatings with novel sensing and catalytical properties. Benefits for society will further be realized from the training of a new generation of researchers knowledgeable in the design, fabrication and application of nucleic acids as building blocks for new emerging materials in many applications that require precise control of assembly as well as chemical and biological functionality.

TECHNICAL SUMMARY

The Hermann lab will design and develop new stimulus-responsive composite materials from self-assembling RNA and DNA modules that contain chemically diverse ligands serving as permanent components to expand functional chemical space or interact with ligands as transiently binding triggers to control assembly and dissociation. Building blocks for the composite materials are RNA-DNA hybrid nanostructures which will be prepared by connecting structurally well-defined RNA motifs as topology-defining joints with diverse DNA modules that provide stable components for modification and inclusion of ligand binding sites.

Partitioning of architectural and functional roles between RNA and DNA components in self-assembling nanostructures provides a new general blueprint for expanding chemical diversity and functionality of nucleic acid hybrid nanomaterials. The new composite nanomaterials will accommodate a variety of DNA modules as unique ligand binding sites for controlled spatial arrangement of chemically diverse ligands, including proteins, small molecules, and metals.

Nucleic acid modules whose stable folding is co-dependent on ligand binding enable the design of nanostructures that assemble under ligand control. Modules that undergo conformational or constitutional changes upon ligand binding will provide devices to trigger dissociation of nanostructures in response to ligands. Connection of RNA-DNA hybrid nanoshapes by a diverse set of nucleic acid linkers will allow controlled assembly of composite materials with surface patterns that retain regularly spaced ligand binding sites of programmable symmetries and feature distances below 10 nm.

Surface patterns created by assembly of RNA-DNA hybrid nanostructures will be modified by selective enzymatic digestion of RNA components and repeat addition of DNA or RNA modules and linkers. This research will establish successive application of additive and subtractive fabrication steps as a novel approach for the preparation of composite nanomaterials that self-assemble from nucleic acid modules and which achieve new properties as functional materials by inclusion of various non-nucleic acid components such as proteins, small molecule ligands, and metals.

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.