CAREER: Programmable Peptide Nucleic Acid Molecules as Building-blocks for Complex Nanostructures

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This Faculty Early Career Development (CAREER) grant supports fundamental studies of the thermodynamic stability, morphology, and mechanics of a new type of nucleic acid nanotechnology built using a synthetic mimic of deoxyribonucleic acid or DNA. The programmability and responsive nature of nucleic acid-based nanostructures, nanomaterials and nanomachines give them the potential to transform nanosensing as well as manufacturing from the nanoscale to the mesoscale. However, without protection, DNA-based nanosystems can be unstable in organic solvents commonly used in polymer and peptide synthesis. This award investigates the processing-formation-mechanics relationships in novel, programmable gamma peptide nucleic acid (gammaPNA)-based materials for use in nanomanufacturing processes that depend on aggressive organic solvent solutions. This project advances the knowledge of nucleic acid self-assembly in the field of advanced manufacturing and has the potential to enable sequence-specific polymer synthesis as well as novel peptide assembly processes in polar organic solvents. The objective of the integrated education plan is to investigate voice assistants for advanced manufacturing education, research, and industrial workforce development. To this end, voice assistants are used in the classroom and in the laboratory for supportive training and education that demonstrates the importance of NIST and ASTM standards for nanomanufacturing.The specific goal of this research is to discover the design rules for building complex nanostructures with a preorganized synthetic DNA mimic. While preliminary studies suggest that gammaPNA can successfully hybridize in harsh environments and form filamentous nanostructures according to molecular programs defined by Watson-Crick base pairing, the morphology and mechanics of these nanostructures appear to be modulated by the solution conditions as well as the structural assembly motif and the gamma chemical modifications. This research investigates the effect of organic solvent type and concentration on the stability of all gammaPNA nanostructures. Using total internal fluorescence microscopy and transmission electron microscopy (TEM), the project investigates how substitution with DNA affects the thermodynamics of formation and melting of hybrid gammaPNA-DNA nanotube structures. Using TEM, the nanoscale morphology and “weave structure” are characterized, and, using persistence length studies, bending stiffness as a function of solvent and proportion of DNA is determined. Finally, the use of micropatterned seed features for templated growth and surface coating with these gammaPNA nanomaterials is investigated. Unlike electronegative DNA-based systems, PNA-based systems have a tendency to stick together forming bundles. By leveraging that distinct characteristic, superstructure formation using not only gammaPNA oligomer sequence but also external conditions like surface hydrophobicity could be controlled.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.