Yuwen Zhang

New motifs in DNA nanotechnology

Recently, we have invested a great deal of effort to construct molecular building blocks from unusual DNA motifs. DNA is an extremely favorable construction medium. The sticky-ended association of DNA molecules occurs with high specificity, and it results in the formation of B-DNA, whose structure is well known. The use of stable-branched DNA molecules permits one to make stick-figures. We have used this strategy to construct a covalently closed DNA molecule whose helix axes have the connectivity of a cube, and a second molecule, whose helix axes have the connectivity of a truncated octahedron. In addition to branching topology, DNA also yields control of linking topology, because double helical half-turns of B-DNA or Z-DNA can be equated, respectively, with negative or positive crossings in topological objects. Consequently, we have been able to use DNA to make trefoil knots of both signs and figure of 8 knots. By making RNA knots, we have discovered the existence of an RNA topoisomerase. DNA-based topological control has also led to the construction of Borromean rings, which could be used in DNA-based computing applications. The key feature previously lacking in DNA construction has been a rigid molecule. We have discovered that DNA double crossover molecules can provide this capability. We have incorporated these components in DNA assemblies that use this rigidity to achieve control on the geometrical level, as well as on the topological level. Some of these involve double crossover molecules, and others involve double crossovers associated with geometrical figures, such as triangles and deltahedra.

Construction of DNA Polyhedra and Knots Through Symmetry Minimization

The goals of supramolecular chemistry include structural control on the nanometer scale comparable to that enjoyed by craft workers on the macroscopic scale.1 The ability to join, couple or weave two molecules together to produce a structure with the same certainty enjoyed by a carpenter, a plumber or a garment worker, would increase greatly the efficiency of materials scientists, chemists, and molecular biologists. Chemists have learned that it is not as simple to create structures from molecules as it is from macroscopic objects: They must rely on intrinsic propensities of precursors, because there are no nails, screws, or threads available to form bonds between atoms. Furthermore, the laws of physics do not permit all conceivable separations of atomic nuclei. In contrast, the components in biological systems often self-assemble spontaneously, by using complementary surfaces to form cohesive structures.

Structural DNA nanotechnology: molecular construction and computation

Structural DNA nanotechnology entails the construction of objects, lattices and devices from branched DNA molecules. Branched DNA molecules open the way for the construction of a variety of N-connected motifs. These motifs can be joined by cohesive interactions to produce larger constructs in a bottom-up approach to nanoconstruction. The first objects produced by this approach were stick polyhedra and topological targets, such as knots and Borromean rings. These were followed by periodic arrays with programmable patterns. It is possible to exploit DNA structural transitions and sequence-specific binding to produce a variety of DNA nanomechanical devices, which include a bipedal walker and a machine that emulates the translational capabilities of the ribosome. Much of the promise of this methodology involves the use of DNA to scaffold other materials, such as biological macromolecules, nanoelectronic components, and polymers. These systems are designed to lead to improvements in crystallography, computation and the production of diverse and exotic materials. Branched DNA can be used to emulate Wang tiles, and it can be used to construct arbitrary irregular graphs and to address their colorability.

Chemical synthesis of nanostructures

The control of structure on the nanoscale relies on intermolecular interactions whose specificity and geometry can be treated on a predictive basis. With this criterion in mind, DNA is an extremely favorable construction medium: The sticky-ended association of DNA molecules occurs with high specificity, and it results in the formation of double helical DNA, whose structure is well known. The use of stable branched DNA molecules permits one to make stick-figures. We have used this strategy to construct a covalently closed DNA molecule whose helix axes have the connectivity of a cube. The molecule has twelve double helical edges; each edge is two helical turns in length, resulting in a hexacatenane, each of whose strands corresponds to a face of the object. The cube has been fabricated in solution, which is inefficient. We have developed a solid-support-based synthetic methodology that is much more effective. The key features of the technique are control over the formation of each edge of the object, and the topological closure of each intermediate. Each edge results from the restriction of two hairpins, which are then ligated together. The isolation of individual objects on the surface of the support permits one to use both symmetric and asymmetric sites in the formation of edges that close polygons. We have used solid-support-based methodology to construct a molecule whose helix axes have the connectivity of a truncated octahedron. This figure has 14 faces, of which six are ideally square and eight are hexagonal; this Archimedean polyhedron contains 24 vertices and 36 edges. Control of topology is strong in this system, but control of 3-D structure remains elusive. Topological control is enhanced by the use of topological protection techniques. Our key aim is the formation of prespecified 2-D and 3-D periodic structures with defined topologies. Applications envisioned include nanomanipulators and scaffolding for molecular electronic devices.