Move over Mona Lisa, here you eat tic-tac-toe . It was just about a year ago that Caltech scientists in the laboratory of Lulu Qian, assistant professor of bioengineering, announced they had used a technique known as DNA origami to create tiles that could be designed to self-assemble into larger nanostructures that carry predesigned patterns . They chose to make the world's smallest version of the iconic Mona Lisa.

The feat was impressive, but the technique had a similar limitation to that of Leonardo da Vinci's oil paints: Once the image was created, it could not be easily changed. Now, the Caltech team has made another leap forward with the technology. They have created new tiles that are more dynamic, allowing the researchers to reshape already-built DNA structures. When Caltech's Paul Rothemund (BS '94) pioneered DNA origami more than a decade ago, I used the technique to build a smiley face.

Microscopic Game

Qian's team can now turn that smile into a frown, and then, if they want, turn that frown upside down. And they have gone even further, to the microscopic game of tic-tac-toe in which players place their X's and O's by adding special DNA tiles to the board.

"We developed a mechanism to program the dynamic interactions between complex DNA nanostructures ," says Qian. "Using this mechanism, we created the world's smallest game board for playing tic-tac-toe, where every move involves molecular self-reconfiguration for swapping in and out hundreds of DNA strands at once."

Putting the Pieces Together

That swapping mechanism combines two previously developed DNA nanotechnologies . It uses the building blocks from one and the general concept from the other: self-assembling tiles, which were used to create the tiny Mona Lisa; and strand displacement, which has been used by Qian's team to build DNA robots.

Both technologies make use of DNA's ability to be programmed through the arrangement of its molecules. Each strand of DNA consists of a backbone and four types of molecules known as bases. These bases – adenine, guanine, cytosine, and thymine, abbreviated as A, T, C, and G – can be arranged in any order, with the order representing information that can be used by cells, or in this case by engineered nanomachines.

"In this work, we invented the mechanism of tile displacement, which follows the abstract principle of strand displacement but it occurs at a larger scale between DNA origami structures," says Qian's former graduate student Philip Petersen (PhD '18), lead author of the study "This is the first mechanism that can be used to program dynamic behaviors in systems of multiple interacting DNA origami structures."