A key feature of natural nanomachines is the ability to change into a variety of shapes in response to diverse yet specific stimuli. But previous attempts to mimic this behaviour have been unable to replicate complex multi-step transformations because shape-shifting DNA nanomachines are typically composed of rigid structures connected by a few mobile regions.

Now, however, a research team from Emory University and Purdue University in the US, and Shanghai University in China, is trying to to close this gap by creating DNA nanomachines that can shape-shift in a fundamentally new way. "Think of the shape-shifting robots in Transformers," says Yonggang Ke, senior author on the study and assistant professor at Emory University. "Transforming from a car to a robot occurs in a complex series of movements. Every part of the machine needs to be able to transform. If a machine only has one moving part, it can’t get much more advanced than a light switch."

The new work, which was reported in Science, is a big step towards creating machines that can undergo similarly complex transformations. The starting point for the researchers was to take a fresh look at a functional unit called the anti-junction, a diamond-shaped intersection of multiple separate strands of DNA.

Anti-junctions have two useful properties. First, they can switch conformations between two energetically equivalent states. This means that the more anti-junctions you can pack into a DNA nanomachine, the more shape-shifting ability the nanomachine will have. Second, when an anti-junction shape-shifts, its neighbouring anti-junctions will shape-shift too. Once the neighbours shape-shift, they will in turn cause their neighbours to shape-shift. A controlled stimulus on one anti-junction can therefore trigger a cascade of transformations throughout the entire nanomachine.

To demonstrate this, the research team created simple DNA nanomachines composed of 20–100 nm-wide rectangular grids of anti-junctions. Using diverse inputs including heat, mechanical stimulation, solvent conditions and a specific DNA "trigger" strand, they showed that they could drive large-scale transformation within the nanomachine. Importantly, they could reverse the transformation using specific inputs (also DNA strands), and lock the nanomachines in partially transformed conformations.

The researchers hope that this technology will one day lead to engineered nanomachines with multiple parallel functions. "Imagine having nanomachines that you can inject into the human bloodstream. Some of them will end up in the kidneys, and based on the kidney biochemical environment will turn into one type of functional machine. Some will end up in the liver and take on a different shape with a different function," said Ke. This work could also have future applications in DNA computing, cellular signaling and biophysics. While such futuristic technology may be a long way away, we’re now one step closer to engineering molecular machines that rival those formed over the last millions of years.