World’s Smallest DNA Tic-Tac-Toe Game Board

Researchers from the California Institute of Technology (Caltech) have developed a new technique for shaping structures out of strands of DNA (DNA origami). In the game of tic-tac-toe on a DNA board, they reshaped an already-constructed DNA structure. The technology could be used to develop more sophisticated nanomachines with reconfigurable parts.

One year ago Caltech scientists in the laboratory of Lulu Qian used a technique known as DNA origami to create world’s smallest Mona Lisa. Now, the Caltech team has made another leap forward with a new technique. Qian’s team played the world’s smallest tic-tac-toe game 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,” Lulu Qian, assistant professor of bioengineering, said in a news release. “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.”

Their mechanism, described in a paper published in the journal Nature Communications, combines two previously developed DNA nanotechnologies. DNA origami technology called self-assembling tiles and strand displacement, which has been used by Qian’s team to build DNA robots.

Both technologies take advantage of the natural tendency of DNA molecules (bases), to pair up with one another. Each base adenine (A), guanine (G), cytosine (C), and thymine (T), can be arranged in any order, with the order representing information that can be used by cells/ nanomachines. The A base pairs with T, C pairs with G, and any sequence of bases will want to pair up with a complementary sequence.

For example, a strand with a molecule sequence GCGATA, pairs perfectly with a CGCTAT strand. A sequence can also pair up with a partially matching sequence. A strand will “dump” a strand that’s a partial match for one that’s a better match. This replacement of one match for a better match is called “strand displacement.” Researchers use these abilities and create shapes out of DNA by manipulating the sequences of the letters.

The technology of self-assembling tiles is easier to explain. It involves the creation of square-shaped tiles of DNA designed to fit together like the pieces of a puzzle. Each tile has its own place in the assembled picture, and it only fits in that spot.

Qian’s team put nine blank DNA tiles designed to form a three-by-three grid into a test tube. Once the tiles self-assembled, the researchers took turns adding X or O tiles to the test tube. X and O tiles were designed to replace specific blank tiles in the grid using strand displacement. The game took six days, with player X emerging as the winner.

“In this work, we invented the mechanism of tile displacement, which follows the abstract principle of strand displacement but occurs at a larger scale between DNA origami structures,” said Philip Petersen, former Qian’s graduate student and 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.”

According to Grigory Tikhomirov, a senior postdoctoral scholar and co-author of the study, research was about far more than just a game. The goal is to develop nanomachines that can be modified or repaired after they have already been built.

“When you get a flat tire, you will likely just replace it instead of buying a new car. Such a manual repair is not possible for nanoscale machines,” said Tikhomirov. “But with this tile displacement process we discovered, it becomes possible to replace and upgrade multiple parts of engineered nanoscale machines to make them more efficient and sophisticated.”

Reshaping DNA structures could be very useful in future. One research group has already developed a molecule-sorting DNA nanorobot. Qian’s team is on a good way too.

Watch an animation made by Qian’s team in the video below:

By Andreja Gregoric, MSc

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