Scientists build tiny structures using Lego-like DNA ‘bricks’

Debuting an invention that even the creative minds that design plain old plastic Lego bricks probably couldn’t have imagined, biologists announced this week that they had figured out a way to make Lego-like bricks from DNA — and to use the teeny-tiny modules to build a variety of different, often intricate, three-dimensional shapes.

Having the capability to build nanoscale structures out of DNA bricks is more than mere play: Someday it could help engineers improve medical devices for drug delivery or components for electronic circuits, among other advances, the team wrote in a study that described the new building method (abstract here), published Thursday in the journal Science.

The paper was the group’s second research document describing a DNA-based building technique in six months. The other study — explaining how senior author Peng Yin and colleagues at Harvard’s Wyss Institute for Biologically Inspired Engineering used a similar strategy to build two-dimensional shapes— was published in the journal Nature in June.

Both the 2D and 3D building methods use single strands of DNA as their basic building blocks. DNA, which stores the genetic blueprint for life, is a long, chain-like molecule composed of nucleotide bases linked together by a sugar backbone. There are four different bases, represented by the letters A, T, C and G. In the familiar double-helix, two complementary strands of DNA line up and twist together. The A bases on one strand bind to T bases on the other, and vice versa; the C bases on one strand bind to G bases on the other, and vice versa.

The Harvard team took advantage of this property to synthesize short strands of DNA whose bases would self-assemble in a laboratory vessel — automatically connecting up with their intended neighbors and binding together to form either a sheet of “tiles” (described in the Nature research) or a solid cube of “bricks” (described in the new paper).

By leaving out particular tiles or bricks destined for particular locations in these “molecular canvases,” the researchers were able to form shapes. Using the 2D tile canvases, which measured about 100 by 100 nanometers, they assembled letters, Chinese characters, emoticons and other forms. (Read the Los Angeles Times story about this work.) The 3D Lego-like cube canvases, made of 10 by 10 by 10 bricks and measuring about 25 by 25 by 27 nanometers, were shaped into blocks with intricate channels and cavities as well as other formations, including a structure that resembled the shape of a tiny space shuttle.

Scientists have been working for years on using DNA to build minute devices that might be used to help deliver drugs or monitor biochemistry, but getting the DNA to assemble correctly has been a challenge. Another promising technique known as DNA origami has also been used to form 3D structures — but it requires engineers to create a new set of building blocks for every new shape. The tile and brick methods are modular: One set of standard building blocks should work for a variety of projects.

DNA origami and tile or brick approaches might be combined to help assemble “advanced functional” devices, wrote chemist Kurt V. Gothelf, of Aarhus University in Denmark, in an accompanying perspective article (summary here.)