Philip S. Lukeman

Nucleic Acid Nanostructures: Bottom-Up Control of Geometry on the Nanoscale

DNA may seem an unlikely molecule from which to build nanostructures, but this is not correct. The specificity of interaction that enables DNA to function so successfully as genetic material also enables its use as a smart molecule for construction on the nanoscale. The key to using DNA for this purpose is the design of stable branched molecules, which expand its ability to interact specifically with other nucleic acid molecules. The same interactions used by genetic engineers can be used to make cohesive interactions with other DNA molecules that lead to a variety of new species. Branched DNA molecules are easy to design, and the can assume a variety of structural motifs. These can be used for purposes both of specific construction, such as polyhedra, and for the assembly of topological targets. A variety of two-dimensional periodic arrays with specific patterns have been made. DNA nanomechanical devices have been built with a series of different triggers, small molecules, nucleic acid molecules and proteins. Recently, progress has been made in self-replication of DNA nano-constructs, and in the scaffolding of other species into DNA arrangements.

Two dimensional PNA/DNA arrays: estimating the helicity of unusual nucleic acid polymersElectronic supplementary information (ESI) available: sequence data, experimental protocols for assembly of the tiles and arrays and gel electrophoresis data demonstrating formation of the tiles. See http://www.rsc.org/suppdata/cc/b4/b401103a/

We extend the generality of nucleic acid-based structural nanotechnology by incorporating non-natural nucleic acids into a DNA double crossover (DX) molecule; visualizing two-dimensional arrays of these DX molecules by Atomic Force Microscopy (AFM) enables us to measure the helical repeat of any heteroduplex sequence capable of forming the outer arms of a DX.

Metallic Nanoparticles Used to Estimate the Structural Integrity of DNA Motifs

Branched DNA motifs can be designed to assume a variety of shapes and structures. These structures can be characterized by numerous solution techniques; the structures also can be inferred from atomic force microscopy of two-dimensional periodic arrays that the motifs form via cohesive interactions. Examples of these motifs are the DNA parallelogram, the bulged-junction DNA triangle, and the three-dimensional-double crossover (3D-DX) DNA triangle. The ability of these motifs to withstand stresses without changing geometrical structure is clearly of interest if the motif is to be used in nanomechanical devices or to organize other large chemical species. Metallic nanoparticles can be attached to DNA motifs, and the arrangement of these particles can be established by transmission electron microscopy. We have attached 5 nm or 10 nm gold nanoparticles to every vertex of DNA parallelograms, to two or three vertices of 3D-DX DNA triangle motifs, and to every vertex of bulged-junction DNA triangles. We demonstrate by transmission electron microscopy that the DNA parallelogram motif and the bulged-junction DNA triangle are deformed by the presence of the gold nanoparticles, whereas the structure of the 3D-DX DNA triangle motif appears to be minimally distorted. This method provides a way to estimate the robustness and potential utility of the many new DNA motifs that are becoming available.

Thermodynamic Analysis of Nylon Nucleic Acids

The stability and structure of nylon nucleic acid duplexes with complementary DNA and RNA strands was examined. Thermal denaturing studies of a series of oligonucleotides that contained nylon nucleic acids (1–5 amide linkages) revealed that the amide linkage significantly enhanced the binding affinity of nylon nucleic acids towards both complementary DNA (up to 26 °C increase in the thermal transition temperature (Tm) for five linkages) and RNA (around 15 °C increase in Tm for five linkages) compared with nonamide linked precursor strands. For both DNA and RNA complements, increasing derivatization decreased the melting temperatures of uncoupled molecules relative to unmodified strands; by contrast, increasing lengths of coupled copolymer raised Tm from less to slightly greater than Tm of unmodified strands. Thermodynamic data extracted from melting curves and CD spectra of nylon nucleic acid duplexes were consistent with loss of stability due to incorporation of pendent groups on the 2′‐position of ribose and recovery of stability upon linkage of the side chains.

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.

Nicks, Nodes, and New Motifs for DNA Nanotechnology

The properties that make DNA such an effective molecule for its biological role as genetic material also make it a superb molecule for nanoconstruction. One key to using DNA for this purpose is to produce stable complex motifs, such as branched molecules. Combining branched species by sticky ended interactions, leads to N- connected stick figures whose edges consist of double helical DNA. Zero node removal or reciprocal crossover, leads to complex fused motifs, such as rigid multi-crossover molecules and paranemic crossover molecules. Multi-crossover molecules have been used to produce 2D arrays and a nanomechanical device. Algorithmic assembly and the use of complex complementarities for joining units are goals in progress that are likely to produce new capabilities for DNA nanotechnology.

Experiments in structural DNA nanotechnology: Arrays and devices

In recent years, the chemistry of DNA has expanded from biological systems to nanotechnology. The generalization of the biological processes of reciprocal exchange leads to stable branched motifs that can be used for the construction of DNA-based geometrical and topological objects, arrays and nanomechanical devices. The information in DNA is the basis of life, but it can also be used to control the physical states of a variety of systems, leading ultimately to nanorobotics; these devices include shape-changing, walking and translating machines. We expect ultimately to be able to use the dynamic information-based architectural properties of nucleic acids to be the basis for advanced materials with applications from nanoelectronics to biomedical devices on the nanometer scale.