DNA Nanotechnology Meets Peptide and Protein Self-Assembly

Self-assembly of DNA, peptides, and proteins provides inherently unique yet essential functionality in biological systems. The inimitable specific binding interaction of DNA, as well as the spontaneous transition of peptide or protein molecules into highly organized superstructures, can be harnessed for sophisticated artificial materials and nanostructure fabrication. Because of their unprecedented programmability and addressability, DNA nanostructures and especially DNA origami nanostructures provide a modular platform for the development of hybrid DNA-peptide and DNA-protein systems. In this Perspective, we discuss how DNA nanostructures can be leveraged to control peptide and protein self-assembly, thus enabling the creation of new and increasingly sophisticated hybrid biomaterials, the single-molecule study of peptide-peptide self-assembly, and the development of therapeutic tools to modulate disease-related amyloid aggregation. Additionally, coiled coil motifs, as an example, can be used as programmable building blocks in DNA nanotechnology for the peptide and protein-mediated hierarchical self-assembly of DNA nanostructures. Finally, we address the potential of DNA nanostructure-templated protein self-assembly. This Perspective highlights current challenges, emerging applications, and future opportunities that are shaping this rapidly growing research area at the interface between nanotechnology, supramolecular chemistry, biomolecular engineering, and biomedicine.