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Integrating protein and peptide self-assembly with DNA nanotechnology

ORAL · Invited

Abstract

The ability to design materials that mimic the complexity and functionality of biological systems is a long standing goal of nanotechnology, with applications in medicine, energy, and fundamental science. Biological molecules such as proteins, peptides, and DNA possess a rich palette of self-assembly motifs and chemical functional diversity, and are attractive building blocks for the synthesis of such nanomaterials. DNA provides unparalleled programmability to build nanostructures, but the resulting materials are limited to the chemical and physical properties of oligonucleotides. Proteins and peptides, by contrast, have a much greater palette of functionality and chemical diversity, but are more difficult to program into arbitrarily complex nanostructures. In this talk, we will describe research in creating hybrid materials that incorporate proteins and peptides with DNA nanotechnology to create various assemblies (cages, nanofibers, addressable nanobots, and 3D crystals) with a high degree of programmability and nanoscale resolution. Key to these endeavors will be (bio)molecular design, chemistry for linking components in a site-specific fashion, and the tuning of multiple self-assembly "modes" to create hybrid structures. Although the talk will focus on the fundamental chemistry and self-assembly of these systems, we will also discuss potential applications in areas such as targeted cargo delivery, biomaterials for regenerative medicine, and synthesis of virus- and antibody-mimetic nanostructures.

Publication: • A. Buchberger, R.P. Narayanan, J. Bernal-Chanchavac, C.R. Simmons, K. Riker, N.E. Fahmi, R. Freeman, N. Stephanopoulos*, "Integrating proteins and DNA nanostructures using orthogonal coiled-coil peptides" (submitted)<br>• R.P. Narayanan, A. Buchberger, L. Zou, N.E. Fahmi, H. Yan, F. Zhang M.J. Webber*, N. Stephanopoulos*, "Supramolecular polymerization of DNA nanostructures using high-affinity host-guest interactions" (submitted)<br>• B. Smolková, T. MacCulloch, T. Rockwood, M. Liu, S.J.W. Henry, A. Frtús, M. Uzhytchak, M. Lunova, M. Hof, P. Jurkiewicz, A. Dejneka, N. Stephanopoulos*, O. Lunov*, "Effect of the protein corona on endosomal escape of functionalized DNA nanostructures" ACS Appl. Mater. Interfaces 2021, 13, 46375–46390.<br>• C.R. Simmonsǂ, T. MacCullochǂ, F. Zhang, Y. Liu, N. Stephanopoulos*, H. Yan*, "Self-Assembly of a DNA Crystal Scaffold Containing Modular Cavities for the Precise Arrangement of Macromolecules" Angew. Chem. Int. Ed. 2020, 59, 18619-18626.<br>• N. Stephanopoulos*, "Hybrid nanostructures from the self-assembly of proteins and DNA" Chem 2020, 6, 364-405.<br>• A. Buchberger, C.R. Simmons, N.E. Fahmi, R. Freeman, N. Stephanopoulos*, "Hierarchical assembly of nucleic acid/coiled-coil peptide nanostructures" J. Am. Chem. Soc. 2020, 142, 1406-1416.<br>• Y. Xu, S. Jiang, C. Simmons, R.P. Narayanan, F. Zhang, A.-M. Aziz, H. Yan, N. Stephanopoulos*, "Tunable nanoscale cages from self-assembling DNA and protein building blocks" ACS Nano 2019, 13, 3545–3554.

Presenters

  • Nicholas Stephanopoulos

    Arizona State University

Authors

  • Nicholas Stephanopoulos

    Arizona State University