Petr Sulc, a researcher at Arizona State University's Biodesign Center for Molecular Design and Biomimetics. Photo: The Biodesign Institute at Arizona State University.
Petr Sulc, a researcher at Arizona State University's Biodesign Center for Molecular Design and Biomimetics. Photo: The Biodesign Institute at Arizona State University.

An impressive array of architectural forms can be produced from the popular interlocking building blocks known as LEGO. All that is needed is a child's imagination to construct a virtually infinite variety of complex shapes.

In a new paper in Physical Review Letters, researchers describe a technique for using LEGO-like elements at the scale of a few billionths of a meter. Further, they are able to cajole these design elements to self-assemble, with each LEGO piece identifying its proper mate and linking up in a precise sequence to create a desired nanostructure.

While the technique described in the new study is simulated on computer, the strategy is applicable to self-assembly methods common to the field of DNA nanotechnology. Here, the equivalent of each LEGO piece consists of nanostructures made out of DNA, the famous molecular repository of our genetic code. The four nucleotides making up DNA – commonly labelled A, C, T and G – stick to one another according to a reliable rule: A nucleotides always pair with Ts and C nucleotides with Gs.

Using these base-pairing properties allows researchers like Petr Sulc, a researcher at Arizona State University's Biodesign Center for Molecular Design and Biomimetics and corresponding author of the new paper, to design DNA nanostructures that can take shape in a test tube, as if on autopilot.

"The possible number of ways how to design interactions between the building blocks is enormous, something that is called a 'combinatorial explosion'," Sulc says. "It is impossible to individually check every possible building block design and see if it can self-assemble into the desired structure. In our work, we provide a new general framework that can efficiently search the space of possible solutions and find the one which self-assembles into the desired shape and avoids other undesired assemblies."

The new technique marks an important step forward in the rapidly developing field of DNA nanotechnology, where self-assembled structures are finding their way into everything from nanoscale tweezers to cancer-hunting DNA robots.

Despite impressive advances, construction methods that rely on molecular self-assembly have had to contend with the unintended binding of building material, and the challenges grow with the complexity of the intended design. In many cases, researchers are perplexed as to why certain structures self-assemble from a given set of elementary building blocks, as the theoretical foundations of these processes are still poorly understood.

To confront this problem, Sulc and his colleagues invented a clever color-coding system that manages to restrict the base pairings to only those appearing in the design blueprint for the final structure, with alternate base-pairings forbidden. This process works through a custom-designed optimization algorithm, where the correct color code for the self-assembly of the intended form produces the target structure at an energy minimum, while excluding competing structures.

Sulc and his colleagues tested this system on a computer, by designing two crystal structures of great importance to the field of photonics: pyrochlore and cubic diamond. The authors note that this innovative method is applicable to any crystal structure.

Together with Hao Yan and Nick Stephanopoulos, colleagues at the Biodesign Center, Sulc now plans to experimentally realize some of the structures they were able to design on computer.

"While the obvious application of our framework is in DNA nanotechnology, our approach is general, and can be also used for example to design self-assembled structures out of proteins," Sulc says.

This story is adapted from material from Arizona State University, with editorial changes made by Materials Today. The views expressed in this article do not necessarily represent those of Elsevier. Link to original source.