Albany 2015:Book of Abstracts
June 9-13 2015
©Adenine Press (2012)
Dynamic DNA devices and assemblies formed by shape-complementary, non-basepairing 3D components(*)
Nucleic acid molecules can bind through weaker interactions than base pairing. Such recognition occurs between RNase P, an RNA-based enzyme, and its substrate, pre-transfer RNA (tRNA), which undergoes cleavage of its 5' leader strand to yield mature tRNA (Guerrier-Takada et al, 1983). Here, we imitate the principle by which RNase P recognizes tRNA using programmable self-assembly with DNA (Jones et al, 2015). We show that discrete 3D DNA components can specifically self-assemble in solution based on shape-complementarity principles and without basepairing. Using this principle, we produced homo- and heteromultimeric objects including micrometer-scale one- and two-stranded filaments and lattices, as well as reconfigurable devices including an actuator, a switchable gear, an unfoldable nanobook, and a nanorobot. These multidomain assemblies were stabilized via short-ranged nucleobase stacking bonds that compete against electrostatic repulsion between the components’ interfaces. Using imaging by electron microscopy, ensemble and single-molecule FRET spectroscopy, and electrophoretic mobility analysis, we show that the balance between attractive and repulsive interactions, and thus the conformation of the assemblies, may be finely controlled by global parameters such as cation concentration or temperature, and by an allosteric mechanism based on strand-displacement reactions. Our shape recognition method expands the palette of potential interactions for DNA-based nanotechnology and adds a layer of abstraction in which components may be treated conceptually as objects that interact in shape space, and not anymore in sequence space. This property enables the design on a higher structural level without having to program the detailed DNA strand sequences for connecting components. We anticipate that our findings will help creating dynamic macromolecular devices and assemblies as scaffolds for various purposes. Specifically, we envision potential applications in advanced therapeutics, biosensing, active plasmonics, and responsive nanostructured materials.
This research has been supported by the Deutsche Forschungsgemeinschaft and the European Research Council.
(*) abstract and title adapted from
T. Gerling, K. Wagenbauer, A. Neuner, & H. Dietz, Science, accepted manuscript