No "sticky ends"? No problem.
A new study by NYU chemists finds that DNA tiles can assemble into 3D structures without the sticky cohesion of hydrogen bonding. This finding, published in Nature Communications , turns a fundamental paradigm in the field of DNA self-assembly on its head.
"We found that changing the shape of the interface between DNA strands yields different assembly outcomes—a demonstration of complex matter obtained by simple design," said study author Simon Vecchioni, a research scientist in NYU's Department of Chemistry.
The late NYU Chemistry Professor Ned Seeman founded the field of DNA nanotechnology, which uses synthetic DNA strands as building blocks to assemble complex architectures. Seeman discovered that DNA could self-assemble into triangular 3D shapes that can co-assemble into crystals if "sticky ends" were added to the end of each DNA double helix, enabling them to attach to one another through hydrogen bonds. This combination of DNA molecules and sticky ends, Seeman wrote , "creates a powerful molecular assembly kit for structural DNA nanotechnology."
In their study in Nature Communications, Seeman's colleagues in the NYU DNA Lab built upon this foundational knowledge. But instead of using sticky ends with hydrogen bonds, they determined that shape alone could guide DNA to assemble like a puzzle.
"With a jigsaw puzzle, you don't need to glue the pieces. You just need the shapes to fit together," said Vecchioni. "And it turns out that the triangle shape that is central to this work is extremely happy to self-assemble without sticky ends."
By leveraging the geometry of two-dimensional subunits of DNA and the flat interface at the end of each double helix, the researchers generated an impressive library of complex, varied 3D structures made entirely out of DNA. Many of the resulting architectures were completely new forms and shapes marked by novel twists, inversions, and rotations.
"We vastly increased the complexity of the material that we're making," said study author Ruojie Sha, a senior research scientist in NYU's Department of Chemistry. "We've put in tiles of a certain geometry and interface, and we let nature figure out the best outcome. In this way, we're learning from a natural form of computing.
Notably, the researchers found that they could control assembly outcomes between traditional "right-handed" DNA and so-called mirror DNA, which is "left-handed." (A DNA helix twists to the right, but a synthetic left-handed version can be made to twist to the left.)
When the researchers made changes at the flat stacking interface, they could get left- and right-handed DNA to avoid each other, mix, or form layered structures—essentially, prompting mirror DNA to communicate and coexist within the same 3D structures.
"The outcome is that we're able to build mirrored materials. But fundamentally, we found a way to exchange information between the mirror world and our world," said Vecchioni. "This means that the debate on mirror life can be kicked down the road, as we can actually use everyday molecules to gain information from mirror ones."
The findings demonstrate the increasingly complex matter that can be created using DNA, laying the groundwork for future DNA-based materials that could revolutionize optical, electronic, and biomedical technologies. For instance, because DNA crystals are made of mostly water, the highly networked structures allow biomolecules to "soak" in and out, which could be particularly useful for creating biosensors or drugs.
Additional study authors include Karol Woloszyn, Andrew Horvath, Mara Jaffe, Lara Perren, Joe Rueb, Samyra Mahiba, Yoel P. Ohayon, and James W. Canary of NYU's Department of Chemistry, as well as Nataša Jonoska of the University of South Florida. The research was supported by the National Science Foundation (GCR-2317843, CCF-2505772, DMS-2054321, CCF-2107267, CCF-2505771, DMR-1420073), Department of Energy (DE-SC0007991), and NASA (80NSSC24K1386).
