Self-assembly of Synthetic Nucleic Acid Nanostructures for the Development of Mechanical Biosensors

The evergrowing need to understand and engineer biological and biochemical mechanisms has led to the emergence of the field of nanobiosensing. Structural DNA nanotechnology, encompassing methods such as DNA origami and single-stranded tiles, involves the base pairing-driven knitting of DNA into discrete one-, two-, and three-dimensional shapes atnanoscale. Such nanostructures enable the versatile design and fabrication of nanobiosensors. These systems benet from DNA's programmability, inherent biocompatibility, and the ability to incorporate and organize functional materials such as proteins and metallic nanoparticles. A mix-and-match taxonomy and approach to designing nanobiosensors using structural DNA nanotechnology, in which the choices of bioanalyte and transduction mechanism are fully independent of each other has led to opportunities for greater complexity and programmability of these systems.

Despite its potential to transform diagnostics, therapeutics, nanomachines, nanosensing, and molecular computation, there are presently no consumer-directed or medical products on the market made from structural DNA nanotechnology. The broader impact of structural DNA nanotechnology has been limited due to restrictions imposed by the scope of DNA as a nanomaterial. Its dependency on high salt concentrations for structural stabilization, susceptibility to enzymatic degradation and denaturation in organic solvents limit the applications of unprotected DNA nanostructures.

In this work, we study the tuneable actuation of twisted, micron-scale DNA nanotubes using a non-scaffolded approach. This study highlights in part, the capability for reversible conformational changes by chiral DNA microstructures which is an emerging area of active research. Additionally, the work would also highlight the need for the development of stiffer

molecular constructs for active architectures at the mesoscale. This work then demonstrates subsequently, the development of nanomaterials made from gamma-modified peptide nucleic acids (gPNA) - a synthetic DNA mimic as a building material for nanofibers. Specifically, gPNA show the capability to enable formation of complex, self-assembling nanostructures in select polar aprotic organic solvent mixtures. We explore and highlight the role of conventional surfactants, solvent conditions and strand substitution with DNA in tuning the morphology of the self-assembled nanostructures. This work thereby introduces a science of gPNA nanotechnology. Finally, we engineer improvements

to the self-assembly process of gPNA to robustly form nanofibers at constant temperatures in as little as 30 minutes. We achieve this by exploring the (L)-serine -modification in the peptide backbone at high densities.