Art and Science: DNA Folds Itself Like Origami to Re-Create Mona Lisa

The process of fractal assembly, using wooden puzzle pieces. Caltech

Updated | Scientists have created the world's tiniest copy of the Mona Lisa using something a little less traditional than oil paints—DNA.

Researchers working at the California Institute of Technology used DNA nanotechnology, also known as DNA origami, to "paint" Leonardo da Vinci's masterpiece. DNA origami involves folding a single long strand of DNA into a predetermined shape, much as one does with paper origami. As Motherboard noted, this Mona Lisa is about .000028 inches across.

A team of scientists working at the lab of Caltech assistant professor of bioengineering Lulu Qian have now created a method that allows that DNA origami to self-assemble. To really make their point, they demonstrated the method's capabilities by DNA origami-ing the Mona Lisa. A paper describing the work was published online Wednesday in the scientific journal Nature.

"We are excited about scaling up DNA origami self-assembly," Qian told Newsweek over email, "because it is now conceivable to build much more sophisticated artificial molecular machines with sizes similar to that of the simplest life form─a bacterium."

While the technique is fun for obvious reasons, this recent breakthrough—DNA that origamis itself—will also be useful for scientists who find it helpful to be able to see their microscopic work on a larger scale. A few weeks before this research was published, MIT reported that DNA origami provided a way to mimic the "scaffold" structure of photosynthesis scientists have been struggling to reproduce artificially.

According to Science, researchers have been twisting DNA into all kinds of shapes since the 1980s. Paul Rothemund, currently a research professor of bioengineering, computing and mathematical sciences at Caltech, pioneered DNA origami in 2006. According to a Caltech press release, he's since used it to make such artworks as a 100-nanometer-wide smiley face (a nanometer is one-billionth of a meter).

Conceptual illustration of DNA origami tiles self-assembling into a life-size portrait of a bacterium. Demin Liu

Each strand of DNA comprises a series of the same four nucleotides: adenine, thymine, guanine, and cytosine, commonly abbreviated as A, T, G, and C. To become a double strand, A nucleotides need to bond with Ts, and Gs with Cs. When a long strand is combined in a test tube with a number of shorter strands, the shorter ones function as "staples" that help the long strand fold over itself into a given shape. Hence, DNA origami.

To make that process autonomous, the Caltech team designed software that processes an image—like the Mona Lisa—and breaks it down into small individual squares. The next step is calculating the right DNA sequence needed to reproduce each square. Lead author Grigory Tikhomirov, a senior postdoctoral scholar at the Qian lab, said in the Caltech press release that they could have done this by giving each tile unique staples around the edges; think of a puzzle where each piece fits only into one correct other piece.

"[B]ut then we would have to have hundreds of unique edges, which would be not only very difficult to design but also extremely expensive to synthesize," Tikhomirov said in the release. "We wanted to only use a small number of different edge staples but still get all the tiles in the right places."

Rendered atomic force microscopy images of the Mona Lisa, a bacterium, and a rooster self-assembled from DNA origami tiles, shown together with the original DNA origami smiley face. Grigory Tikhomirov, Philip Petersen, and Lulu Qian / Caltech

To achieve this, the team put each tile together in stages, the way you put together a really big puzzle by breaking it down into sections and eventually putting those sections together themselves.

The researchers call this practice "fractal assembly." Their software tool is available online for the benefit of other molecular scientists. The Caltech statement noted that it's already been used to draw a "life-sized portrait of a bacterium and a bacterium-sized portrait of a rooster."

Correction: An earlier version of the story stated the DNA origami depiction of the Mona Lisa measured .0024 inches across. The correct measurement is .000028.