(39d) Self-Assembled Hybrid Peptide-DNA and Protein-DNA Nanostructures

The ultimate goal of nanotechnology is to build structures on the 10-100 nm length scale, with control of matter down to the atomic level. In recent years, DNA has emerged as a powerful molecular building block for the construction of nanostructure materials due to the specificity of Watson-Crick pairing. However, DNA nanostructures are limited by the physical and chemical properties of oligonucleotides, which can be a hindrance for biological applications, or for attaining higher resolution placement of synthetic functionality. Proteins and peptides, by contrast, are the natural “language” of biology, possess a greater diversity of chemical groups, and can position materials sub-nanometer precision. In this work, we present the novel integration of two self-assembling polypeptide motifs with DNA nanostructures: 1) the coiled-coil, and 2) hetero-trimeric proteins. We have synthesized peptide- and protein-DNA conjugates with high site-specificity, allowing us to integrate these components with self-assembled DNA structures with high precision. DNA tiles, wireframe cages, and DNA origami were modified in specific locations with one of two heterodimeric coiled coil peptides that bind with sub-nanomolar affinity. The coiled coil interaction drove the hierarchical assembly of these components into dimers and one-dimensional nanofibers, providing an orthogonal assembly “code” to DNA hybridization. In addition, we will demonstrate the assembly of hierarchically-ordered 3D cages comprised of trimeric protein vertices with tunable DNA arms linking them. These materials are the first to our knowledge to integrate synthetic, self-assembling peptide/protein-DNA hybrids with well-established DNA motifs, and demonstrate the potential of protein-DNA nanotechnology.