PerspectiveChemistry

Functional DNA Origami Devices

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Science  16 Nov 2012:
Vol. 338, Issue 6109, pp. 890-891
DOI: 10.1126/science.1231024

DNA is central to the existence of all life on Earth and uniquely encodes the instructions for producing such life. But it has another set of remarkable properties shared by a much larger class of molecules, most of which are yet to be invented. These “chemically sequenced polymers” (CSPs) are built by adding distinct monomers one at a time and can be programmed in such a way as to assemble into arbitrarily complex and three-dimensional shapes. Nature is far ahead of us in the creation and utility of such molecules, but on page 932 of this issue, Langecker et al. (1) provide a glimpse of the structural precision and functionality they offer for programmed assembly.

When the monomer units of a CSP are nucleic acids, the engineering of such structures is called DNA origami (2, 3) after the Japanese art of paper folding. Here, different parts of a long single-stranded DNA segment are brought and “stapled” together using smaller oligonucleotides that are programmed to hybridize at key locations in the structure. In this way, one can staple and fold the system into any three-dimensional shape.

CSPs are also used in protein folding and engineering, where amino acids are the sequencing elements; however, creation of programmable, functional devices with amino acids would require the ability to predict protein folding under different condition. The original attempts to create synthetic CSPs are simplistic by comparison, but the field of multiblock polymers (4) highlights how elegant order can be generated from just a handful of sequenced “bases” represented by the distinct polymer blocks. Scientists are only just beginning to understand self-assembly and the connections between these various materials (5).

Membrane docking channel from DNA origami.

(A) Cartoon of the DNA origami channel reported by Langecker et al. The channel has two parts, an extramembrane mouth (gray/orange) and a hydrophobic stem (red) extending into the membrane and can control the transport of a range of molecules. (B) Channel structure in averaged negative stain TEM images (1).

CREDIT: FROM (1)

To underscore the point, Langecker et al. report a stunning advance toward programmable structure and function. Using DNA origami, they have designed and synthesized a working ion channel that can spontaneously assemble into a lipid bilayer. The design is derived from α-hemolysin (a protein that is excreted by Streptococcus bacteria to perforate a target cell, causing it to leach iron through the resulting channel for the bacterium to consume) (6). In the resulting device (see the figure), one part of the DNA is folded into a hydrophobic barrel that inserts itself into a nearby lipid bilayer membrane. An extramembrane portion on top of the barrel forms the mouth of the channel.

The level of complexity and function of this device is remarkable, as the TEM images and electrochemical measurements confirm. Once immobilized in a target membrane, the ion channel demonstrates gating behavior when an electrical potential is placed across it. The observed stochastic fluctuations in ion current resemble those seen in many biological (6) and synthetic (7) ion channels. The channel can also transport and recognize DNA hairpins passing through the pore and distinguish differing DNA lengths; furthermore, it has impressive stability commensurate with that of biological ion channels. The possibilities with this system are endless, because one can vary the sequence and corresponding structure quite easily, analogous to site-directed mutagenesis in biology.

A CSP such as DNA also allows one to create nanoparticles and nanowires with broken symmetry—placing chemical groups at specific locations, as opposed to uniformly about an axis of symmetry—because each site of the sequence is addressable. This is no small task. An organic chemist knows how to brominate, say, a specific position on a benzene ring. But symmetry breaking of nanostructures is nearly impossible using existing methods. Yet it is the key to introducing the complexity necessary to create nanomachines with any sophistication.

Acuna et al. recently achieved such symmetry breaking (8). They constructed a DNA origami scaffold that allows the precise placement of two equally sized plasmonic Au nanoparticles on either side of a DNA nanopillar. Optical excitation of the particle pair amplifies the local electromagnetic field hundreds of times. The resulting “nanoantenna” can record the fluctuations of single dye molecules, as well as the binding and unbinding of probe DNA segments. In this example, the broken symmetry of the scaffold, made possible by the sequence-addressable boundaries in DNA origami, enables the colocalization of several components in a way that offers precision, function, and utility.

It is not surprising that DNA is the first system for which humans have realized the potential of CSPs. Powerful tools such as the polymerase chain reaction and DNA sequencing provide unprecedented ability to program, synthesize, and error-check DNA sequences. Biotechnology has increased the production scale and lowered the cost of all forms of DNA and RNA. These advances were driven, in large part, by the special function of DNA as a biological information carrier. A spoil of that enormous effort is the ability to create nanomachines of exceeding complexity. DNA origami and the larger yet unrealized field of chemically sequenced polymers promise a vast array of amazingly programmed structures, of which Langecker et al. and Acuna et al. have given us the first of what will be many examples.

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