Scientists Piece Together DNA Mosaic Creating Smallest Mona Lisa
Her tricky smile and timeless allure have inspired academic study and artistic emulation for more than five centuries. But the story of this perplexing portrait is even richer than it looks. Also, what many don’t know or expect is the small size of the portrait. Mona Lisa’s influence in culture is massive, but the oil-on-wood panel painting measures only about 30 by 21 inches and weighs 18 pounds.
However, in comparison to this new copy in discussion made by researchers from the California Institute of Technology, it seems almost gigantic. This copy was made of … DNA and is the smallest known copy of the work.
The research team used a process that’s known as DNA origami which enables you to fold gene strands into two- and three-dimensional shapes. DNA is best known for encoding genetic data but it’s also a pretty versatile chemical building block.
The Caltech researchers created software that can take an image and break it up into microscopic square sections and identify the DNA sequences needed to develop those squares
. Next, they had to manipulate those sections to get them to self-assemble into a structure that can reassemble the final image.In 2006, Caltech’s Paul Rothemund developed a method to fold a long strand of DNA into a prescribed shape. The technique, dubbed DNA origami, enabled scientists to create self-assembling DNA structures that could carry any specified pattern, such as a 100-nanometer-wide smiley face. DNA origami revolutionized the field of nanotechnology, opening up possibilities of building tiny molecular devices or “smart” programmable materials.
The key to doing this task was to assemble the tiles in stages like assembling small regions of a puzzle. They then joined those regions together to make larger areas, finally putting them together to make the complete puzzle.
Grigory Tikhomirov, senior postdoctoral scholar and lead author of the new study said, “We could make each tile with unique edge staples so that they could only bind to certain other tiles and self-assemble into a unique position in the superstructure. But 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. We wanted to only use a small number of different edge staples but still get all the tiles in the right places.”
To make a single square of DNA origami, the team needs a long single strand of DNA and many shorter single strands, called staples. These are designed to bind to multiple designated places on the long strand.
When the short staples and the long strand are combined in a test tube, the staples pull regions of the long strand together, causing it to fold over itself into the desired shape. A large DNA canvas is assembled out of many smaller square origami tiles. Molecules can be selectively attached to the staples in order to create a raised pattern that can be seen using atomic force microscopy.
The edges of the pieces are the same, but because they are assembled in stages, there is no risk of a tile being put in the wrong place. This means there is no risk, for example, of one corner tile attaching in the wrong corner. The team has called the method ‘fractal assembly’ because, as with abstract mathematical objects called fractals, the same set of assembly rules is applied at different scales. This means that the same rules govern the construction of a puzzle, no matter what its size.
“Once we have synthesized each individual tile, we place each one into its own test tube for a total of 64 tubes,” says Philip Petersen, a graduate student and co-first author on the paper. “We know exactly which tiles are in which tubes, so we know how to combine them to assemble the final product. First, we combine the contents of four particular tubes together until we get 16 two-by-two squares. Then those are combined in a certain way to get four tubes each with a four-by-four square. And then the final four tubes are combined to create one large, eight-by-eight square composed of 64 tiles. We design the edges of each tile so that we know exactly how they will combine.”
The team’s final structure was 64 times larger than the original DNA origami structure designed originally by Rothemund in 2006. Remarkably, thanks to the recycling of the same edge interactions, the number of different DNA strands required for the assembly of this DNA superstructure was about the same as for Rothemund’s original origami. This should make the new method similarly affordable.
“The hierarchical nature of our approach allows using only a small and constant set of unique building blocks, in this case DNA strands with unique sequences, to build structures with increasing sizes and, in principle, an unlimited number of different paintings,” says Tikhomirov. “This economical approach of building more with less is similar to how our bodies are built. All our cells have the same genome and are built using the same set of building blocks, such as amino acids, carbohydrates, and lipids. However, via varying gene expression, each cell uses the same building blocks to build different machinery, for example, muscle cells and cells in the retina.”
The team also created software to enable scientists everywhere to create DNA nanostructures using fractal assembly.
“To make our technique readily accessible to other researchers who are interested in exploring applications using micrometer-scale flat DNA nanostructures, we developed an online software tool that converts the user’s desired image to DNA strands and wet-lab protocols,” says Lulu Qian, assistant professor of bioengineering at Caltech. “The protocol can be directly read by a liquid-handling robot to automatically mix the DNA strands together. The DNA nanostructure can be assembled effortlessly.”
As you can use a combination of software and automatic liquid handling to make these mini paintings, you’re really just limited by your creativity- the team also ‘drew’ portraits of bacteria and a rooster to show what was possible. And that, in turn, could lead to more practical uses.
This work may not be big enough to hang in the Louvre but the nanosized Mona Lisa recreation could provide a scientific breakthrough that has long-reaching benefits.
DNA-based nanostructures like this could help build extremely dense circuits, exotic organic materials or just tests for chemical and molecular interactions.
