Challenges and Applications for Self-Assembled DNA Nanostructures

DNA self-assembly is a methodology for the construction of molecular scale structures. In this method, arti cially synthesized single stranded DNA self-assemble into DNA crossover molecules (tiles). These DNA tiles have sticky ends that preferentially match the sticky ends of certain other DNA tiles, facilitating the further assembly into tiling lattices. We discuss key theoretical and practical challenges of DNA selfassembly, as well as numerous potential applications. The self-assembly of large 2D lattices consisting of up to thousands of tiles have been recently demonstrated, and 3D DNA lattices may soon be feasible to construct. We describe various novel DNA tiles with properties that facilitate self-assembly and their visualization by imaging devices such as atomic force microscope. We discuss bounds on the speed and error rates of the various types of self-assembly reactions, as well as methods that may minimize errors in self-assembly. We brie y discuss the ongoing development of attachment chemistry from DNA lattices to various types of molecules, and consider application of DNA lattices (assuming the development of such appropriate attachment chemistry from DNA lattices to these objects) as a substrate for: (a) layout of molecular electronic circuit components, (b) surface chemistry, for example ultra compact annealing arrays, (c) molecular robotics; for manipulation of molecules using molecular motor devices. DNA self-assembly can, using only a small number of component tiles, provide arbitrarily complex assemblies. It can be used to execute computation, using tiles that specify individual steps of the computation. In this emerging new methodology for computation: -input is provided by sets of single stranded DNA that serve as nucleation sites for assemblies, and ? Contact address: Department of Computer Science, Duke University, Box 90129, Durham, NC 27708-0129. E-mail: [email protected]. John Reif is supported by Grants NSF/DARPA CCR-9725021, CCR-96-33567, NSF IRI9619647, ARO contract DAAH-04-96-1-0448, and ONR contract N00014-99-1-0406. Nadrian C. Seeman is supported by Grants GM-29554, from the National Insititute of General Medical Sciences; N00014-98-1-0093, from the O ce of Naval Research; NSF-CCR-97-2502 from DARPA/NSF; F30602-98-C-0148, from the Air Force Research Laboratory at Rome, NY; and CTS-9986512 from the National Science Foundation. A postscript version of this paper is at URL http://www.cs.duke.edu/ reif/paper/SELFASSEMBLE/selfassemble.ps . -output can be made by the ligation of reporter strands of DNA that run though the resulting assembly, and then released by denaturing. DNA self-assembly can be used to execute massively parallel computations at the molecular scale, with concurrent assemblies that may execute computations independently. Due to the very compact form of DNA molecules, the degree of parallelism (due to distinct tiling assemblies) may be up to 10 to possibly 10. We describe various DNA tiling assemblies that execute various basic computational tasks, such as sequences of arithmetic and logical computations executed in massively parallel fashion. We also consider extensions of these computational methods to 3D DNA tiling lattices and to assemblies that hold state.