Algorithmic Self-Assembly of DNA: Theoretical Motivations and 2D Assembly Experiments.

Abstract Biology makes things far smaller and more complex than anything produced by human engineering. The biotechnology revolution has for the first time given us the tools necessary to consider engineering on the molecular level. Research in DNA computation, launched by Len Adleman, has opened the door for experimental study of programmable biochemical reactions. Here we focus on a single biochemical mechanism, the self-assembly of DNA structures, that is theoretically sufficient for Turing-universal computation. The theory combines Hao Wang's purely mathematical Tiling Problem with the branched DNA constructions of Ned Seeman. In the context of mathematical logic, Wang showed how jigsaw-shaped tiles can be designed to simulate the operation of any Turing Machine. For a biochemical implementation, we will need molecular Wang tiles. DNA molecular structures and intermolecular interactions are particularly amenable to design and are sufficient for the creation of complex molecular objects. The structure of individual molecules can be designed by maximizing desired and minimizing undesired Watson-Crick complementarity. Intermolecular interactions are programmed by the design of sticky ends that determine which molecules associate, and how. The theory has been demonstrated experimentally using a system of synthetic DNA double-crossover molecules that self-assemble into two-dimensional crystals that have been visualized by atomic force microscopy. This experimental system provides an excellent platform for exploring the relationship between computation and molecular self-assembly, and thus represents a first step toward the ability to program molecular reactions and molecular structures.