DNA nanotechnology builds 3D forms with complex curves (includes video)

Since Paul Rothemund’s scaffolded DNA origami procedure was first cited here, it has provided scaffolds for a number of advances in structural DNA nanotechnology, from positioning DNA devices to cooperate or organizing functional components to building boxes with lids. Thanks to Stuart Scott for pointing to this Arizona State University news release announcing an important extension of this technique to 3D DNA nanostructures with complex curvatures. From “New DNA nanoforms take shape” by Richard Harth:

Miniature architectural forms – some no larger than viruses – have been constructed through a revolutionary technique known as DNA origami. Now, Hao Yan, Yan Liu and their colleagues at ASU’s Biodesign Institute have expanded the capability of this method to construct arbitrary, two- and three-dimensional shapes, mimicking those commonly found in nature.

Such diminutive forms may ultimately find their way into a wide array of devices, from ultra-tiny computing components to nanomedical sentries used to target and destroy aberrant cells or deliver therapeutics at the cellular or even molecular level.

In today’s issue of Science [abstract], the Yan group describes an approach that capitalizes on (and extends) the architectural potential of DNA. The new method is an important step in the direction of building nanoscale structures with complex curvature – a feat that has eluded conventional DNA origami methods. …

“Our goal is to develop design principles that will allow researchers to model arbitrary 3-D shapes with control over the degree of surface curvature. In an escape from a rigid lattice model, our versatile strategy begins by defining the desired surface features of a target object with the scaffold, followed by manipulation of DNA conformation and shaping of crossover networks to achieve the design,” Liu said.

To achive this idea, Yan’s graduate student Dongran Han began by making simple 2-D concentric ring structures, each ring formed from a DNA double helix. The concentric rings are bound together by means of strategically placed crossover points. These are regions where one of the strands in a given double helix switches to an adjacent ring, bridging the gap between concentric helices. Such crossovers help maintain the structure of concentric rings, preventing the DNA from extending. …

Varying the number of nucleotides between crossover points and the placement of crossovers allows the designer to combine sharp and rounded elements in a single 2-D form …

The network of crossover points also can be designed in such a way as to produce combinations of in-plane and out-of-plane curvature, allowing for the design of curved 3D nanostructures. While this method shows considerable versatility, the range of curvature is still limited for standard B form DNA, which will not tolerate large deviations from its preferred configuration – 10.5 base pairs/turn. However, as Jeanette Nangreave, one of the paper’s co-authors, explains, “Hao recognized that if you could slightly over twist or under twist these helices, you could produce different bending angles.”

Combining the method of concentric helices with such non-B-form DNA (with 9-12 base pairs/turn), enabled the group to produce sophisticated forms, including spheres, hemispheres, ellipsoid shells and finally—as a tour de force of nanodesign – a round-bottomed nanoflask, which appears unmistakably in a series of startling transmission electron microscopy images …

Yan hopes to further expand the range of nanoforms possible through the new technique. Eventually, this will require longer lengths of single-stranded DNA able to provide necessary scaffolding for larger, more elaborate structures. He credits his brilliant student (and the paper’s first author) Dongran Han with a remarkable ability to conceptualize 2-D and 3-D nanoforms and to navigate the often-perplexing details of their design. Ultimately however, more sophisticated nanoarchitectures will require computer-aided design programs – an area the team is actively pursuing.

The successful construction of closed, 3-D nanoforms, such as the sphere, has opened the door to many exciting possibilities for the technology, particularly in the biomedical realm. Nanospheres could be introduced into living cells for example, releasing their contents under the influence of endonucleases or other digestive components. Another strategy might use such spheres as nanoreactors – sites where chemicals or functional groups could be brought together to accelerate reactions or carry out other chemical manipulations.

These 3D structures are large and complex compared with the 2.0 nm diameter of the DNA double helix. PowerPoint slides of several figures from the Science paper can be downloaded without a subscription. One of these shows the sphere to be 42 nm in diameter, the prolate ellipsoid to be 35 nm by 66 nm, and the round-bottomed nanoflask to be 40 nm wide and 70 nm tall.

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