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World’s Tiniest Tic-Tac-Toe Game Is Made of DNA Tiles

Brought to you by the creators of the mini ‘Mona Lisa’, the game offers a dynamic, rather than static, way to manipulate microscopic structures

It took six days for the scientists to complete the game. Eventually, X emerged victorious (Caltech)
smithsonian.com

The world’s tiniest game of Tic-Tac-Toe is played using DNA and takes six days to complete, but the game was about much more than simply crowning a winner, Kristin Houser explains for Futurism.

The new technique used to create the game allows scientists to freely rearrange DNA structures—something that hadn’t been easily done before. And the technology behind this DNA manipulation has real-world implications, as researchers are currently developing and fine-tuning DNA nanotechnology capable of completing such tasks as delivering drugs and organizing molecular cargo.

DNA consists of four base molecules called adenine, cytosine, guanine and thymine (A, C, G and T). A tends to pair with T, while C pairs with G. A strand of ATTAGCA, for example, would therefore pair with TAATCGT, as Jennifer Ouellette writes for Ars Technica. Researchers from the California Institute of Technology, or Caltech, drew on these established DNA pairing patterns to manipulate strands and force them into various Tic-Tac-Toe-related shapes, the team reports in a recent Nature Communications study.

The technique, known as DNA origami, enabled researchers to “paint” the world’s smallest version of Leonardo da Vinci’s “Mona Lisa” in 2017, but it came with certain drawbacks—namely locking DNA strands into place and preventing researchers from manipulating their shape further, as Futurism’s Houser explains.

The Tic-Tac-Toe game circumvents this complication by using a second technique called DNA strand displacement. With this approach, scientists again exploit DNA pairing patterns. A DNA strand of ATTAGCA, for instance, will abandon a partial match of TAATACC for a full—or, if not available, simply better—match.

In the paper, the researchers compare strand displacement to dating, or rather the lengthy process of choosing and replacing a partner based on shared interests.

It works something like this: Consider a pair named Jenna and Joel. Both love watching foreign language films, chowing down on international cuisine and playing fetch with their pet dogs. But along comes James, an individual who not only enjoys all of the above activities, but also shares Jenna’s penchant for painting. Lured away by this additional shared passion, Jenna ditches Joel for James. In this scenario, Joel is now the displaced strand, unhitched and alone.

In the game, DNA strand displacement works in conjunction with self-assembling tiles, a more straightforward technology that finds square game board pieces lined with specific DNA strands acting much like jigsaw puzzle pieces. “Each tile has its own place in the assembled picture” of a 3x3 grid, a Caltech press statement notes, “and it only fits in that spot.”

According to New Atlas’ Michael Irving, players—in this case the scientists—swapped out these nine blank game board tiles for pieces marked with either an X or an O. To do so, they simply introduced a “marked” tile with a stronger bond than the existing blank tile; an X tile placed in the top left-hand corner, for instance, might offer a perfect pairing for the blank tiles it surrounds, thereby allowing a player to replace a blank tile bearing only a partial match. Each player received nine tiles, one for each place on the board, and each tile fit into just one spot.

In the end, the game lasted six days (as Irving notes, it takes time for the DNA strands to bond and unbond). The X player emerged victorious, creating a perfect storm of three X tiles across the bottom of the board.

"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," study co-author Grigory Tikhomirov says in the statement. "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."

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