A team of scientists at Caltech has created the smallest version of the Mona Lisa ever — out of DNA. The work is described in a paper appearing in the journal Nature.
DNA rendering of Leonardo da Vinci’s Mona Lisa viewed with atomic force microscopy. Image credit: Tikhomirov et al.
In 2006, Caltech Professor Paul Rothemund developed a method, called ‘DNA origami,’ to fold a long strand of DNA into a prescribed shape.
Now, Caltech researcher Dr. Lulu Qian and colleagues have developed an inexpensive method by which DNA origami self-assembles into large arrays with entirely customizable patterns, creating a sort of canvas that can display any image.
“While DNA is perhaps best known for encoding the genetic information of living things, the molecule is also an excellent chemical building block,” the authors explained.
“A single-stranded DNA molecule is composed of smaller molecules called nucleotides — abbreviated A, T, C, and G — arranged in a string, or sequence.”
“The nucleotides in a single-stranded DNA molecule can bond with those of another single strand to form double-stranded DNA, but the nucleotides bind only in very specific ways: an A nucleotide with a T or a C nucleotide with a G. These strict base-pairing ‘rules’ make it possible to design DNA origami.”
“To make a single square of DNA origami, one just needs a long single strand of DNA and many shorter single strands — called staples — 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, like putting together a puzzle. Molecules can be selectively attached to the staples in order to create a raised pattern that can be seen using atomic force microscopy.”
To demonstrate their method, called ‘fractal assembly,’ Dr. Qian and co-authors created the world’s smallest recreation of Leonardo da Vinci’s Mona Lisa.
“We developed software that can take an image such as the Mona Lisa, divide it up into small square sections, and determine the DNA sequences needed to make up those squares,” they explained.
“Next, our challenge was to get those sections to self-assemble into a superstructure that recreates the Mona Lisa.”
“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,” said Dr. Grigory Tikhomirov, lead author of the study.
“We wanted to only use a small number of different edge staples but still get all the tiles in the right places.”
“The key to doing this was to assemble the tiles in stages, like assembling small regions of a puzzle and then assembling those to make larger regions before finally putting the larger regions together to make the completed puzzle.”
“Each mini puzzle utilizes the same four edges, but because these puzzles are assembled separately, there is no risk, for example, of a corner tile attaching in the wrong corner.”
The team’s final structure was 64 times larger than the original DNA origami structure designed by Professor 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 Professor Rothemund’s original origami.
“This should make the new method similarly affordable,” Dr. Qian noted.
Using software tool and automatic liquid-handling techniques, several other patterns were designed and assembled from DNA strands, including a life-sized portrait of a bacterium and a bacterium-sized portrait of a rooster.
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Grigory Tikhomirov et al. 2017. Fractal assembly of micrometre-scale DNA origami arrays with arbitrary patterns. Nature 552: 67-71; doi: 10.1038/nature24655
