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Hierarchical assembly of DNA origami structures : theoretical aspects and biological applications

Pfeifer, Wolfgang ORCID

Nature uses hierarchical self-assembly to realize fascinating structures with complex architectures from rather simple building blocks. Utilizing this approach, emergent properties arise which are surpassing the sum of properties from the individual components and are inherently coupled to the building blocks and the forces linking them together. Since the advent of structural DNA nanotechnology, scientists strive to realize artificial structures with ever growing complexity and functionality. DNA origami is a method of choice for the bottom-up assembly of biomimetic systems, as it allows the precise and programmable hierarchical self-assembly at the nanoscale, coupled with sub-nanometer spatial resolution. In this work, the hierarchical self-assembly of different macromolecular structures is guided by programmable DNA interactions and used to construct several different homo- and heterooligomeric systems. The emulation of protein filaments is performed by designing and creating a highly modular DNA origami building block, which can undergo dimerization and multimerization reactions, depending on the addressed interfaces, eventually resulting in more than 15 different filamentous structures with distinct ultrastructures and global elastic properties. The synthetic DNA filaments were analyzed by microscopic data, showing the successful realization of artificial, biomimetic structures with persistence lengths similar to – or even larger than – those of natural protein filaments. Furthermore, a nanocage for the compartmentalized spatial confinement of proteins and nanoparticles is designed and realized by using the DNA origami approach. By using hierarchical self-assembly, the pathway to a defined multi-compartments system can be well defined and thus allows a multitude of different final structures to be realized. For this purpose, all fundamental units are pre-assembled into reactive species, dimerized and finally characterized by single-particle and ensemble methods. Both temperature and cation concentration are tuned to precisely control the fate of the system.

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Pfeifer, Wolfgang: Hierarchical assembly of DNA origami structures. theoretical aspects and biological applications. 2019.

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