Training DNA for the nano assembly line
Harvard biologists have brought new meaning to the term “fine print” by devising microscopic tiles made of DNA that self-assemble into letters, Chinese characters, emoticons and other shapes.
More than mere doodling, their advance, detailed this week in the journal Nature, could make it easier and cheaper to build tiny DNA devices capable of delivering drugs or aiding the study of biochemistry, scientists said.
“This technique will accelerate the research field of DNA nanotechnology,” said Ebbe Sloth Andersen, a researcher at Aarhus University in Denmark who collaborated on an editorial that accompanied the report.
In its usual role as a warehouse for storing genetic information, DNA helps build humans and hummingbirds, maple trees and meerkats — all sorts of complex organisms. But as a building material for machines smaller than the smallest bacterium, it has been tough to control.
Since the early 1980s, engineers have experimented with a variety of approaches to create structures out of DNA, including the use of tiles — small bricks woven together out of several strands of DNA — that could stick to one another and selfassemble into shapes.
But when researchers tried to construct precisely defined shapes, they ran into trouble, said Peng Yin, a systems biologist at Harvard’s Wyss Institute in Boston and senior author of the Nature study. The tiles tended to stick together incorrectly, resulting in incomplete structures.
“People thought this couldn’t work,” Yin said.
But he and his collaborators pressed on, ultimately designing bricks out of single — rather than multiple — strands of DNA.
The strands each had four sequences of 10 or 11 bases, which could bind to complementary sequences of 10 or 11bases on other tiles. If all four sequences on the edges of a tile bind with their matching counterparts on neighboring tiles, the tile assumes a rectangular shape.
The scientists programmed the tiles to stack up in a staggered formation, like a miniature brick wall. Then they created shapes by leaving out tiles at certain locations of their 64-by-103nanometer “molecular canvas.”
Yin compared the process to a group of people who figure out how to form a line when each of them knows only who they’re supposed to be behind: Person No. 2 knows he should follow person No. 1, person No. 3 knows she should follow person No. 2, and so on.
Similarly, for every tile on the Harvard team’s canvas, each linking edge should connect only with its perfect complement, Yin said.
“You just mix these 1,000 different molecules, and they know how to combine,” he said. “There’s only one position for them to fit.”
Using the technique, the team initially attempted to construct 110 shapes. All but seven of them assembled properly.
The holdouts included the “@” sign, a hollow “H” and two Chinese characters. The researchers managed to successfully redesign four of the shapes.
To speed the assembly process, team members wrote a computer program that could analyze images and figure out which mix of edges would be necessary to get the modular tiles to selfassemble properly. They used a robot to pick the correct tiles to use in each batch.
The technique is “quite amazing,” said Hao Yan, a professor at the Biodesign Institute at Arizona State University in Tempe who was not involved in the research.
It also could turn out to be quite efficient, because different combinations of the same tiles can create different shapes, Andersen said.