Molecular Assembly and Computation: From Theory to Experimental Demonstrations

While the topic of Molecular Computation would have appeared even a half dozen years ago to be purely conjectural, it now is an emerging sub eld of computer science with the development of its theoretical basis and a number of moderate to large-scale experimental demonstrations. This paper focuses on a subarea of Molecular Computation known as DNA self-assembly. Self-assembly is the spontaneous self-ordering of substructures into superstructures driven by the selective aÆnity of the substructures. DNA provides a molecular scale material for e ecting this programmable self-assembly, using the selective aÆnity of pairs of DNA strands to form DNA nanostructures. DNA self-assembly is the most advanced and versatile system known for programmable construction of patterned systems on the molecular scale. The methodology of DNA self-assembly begins with the synthesis of singlestrand DNA molecules that self-assemble into macromolecular building blocks called DNA tiles. These tiles have sticky ends that match the sticky ends of other DNA tiles, facilitating further assembly into large structures known as DNA tiling lattices. In principal you can make the DNA tiling assemblies form any computable twoor three-dimensional pattern, however complex, with the appropriate choice of the tiles component DNA. This paper overviews the evolution of DNA self-assembly techniques from pure theory to experimental practice. We describe how some theoretical developments have made a major impact on the design of self-assembly experiments, as well as a number of theoretical challenges remaining in the area of DNA self-assembly. We descuss algorithms and software for the design, simulation and optimization of DNA tiling assemblies. We also describe the rst experimental demonstrations of DNA self-assemblies that execute molecular computations and the assembly of patterned objects at the molecular scale. Recent experimental results indicate that this technique is scalable. Molecular imaging devices such as atomic force microscopes and transmission electron microscopes allow visualization of self-assembled two-dimensional DNA tiling lattices composed of hundreds of thousands of tiles. These assemblies can be used as sca olding on which to position molecular electronics and robotics components with precision and speci city. The programmability lets this sca olding have the patterning required for fabricating complex devices made of these components. ? Contact address: Department of Computer Science, Duke University, Box 90129, Durham, NC 27708-0129. E-mail: [email protected]. John Reif is supported by DARPA/AFSOR Contract F30602-01-2-0561, NSF ITR Grant EIA-0086015, DARPA/NSF Grant CCR-9725021.