Unravelling DNA to create a new generation of topologically active materials
By combining our knowledge of polymer physics and molecular biology, scientists can craft DNA-based soft materials that can change properties over time.
DNA is essentially a long polymer consisting of four different types of monomers – the nucleotides A, T, C and G, which stack together into base pairs. Like all polymers, DNA chains can get entangled at high concentrations. In fact, they get so tied up that a single human cell can store up to 2m of DNA crammed into its nucleus, an object just 10μm in size.
If DNA molecules stayed horribly entangled, there would be a problem: it would be impossible for chromosomes – long pieces of DNA containing millions of base pairs – to be constantly read and copied. And if that didn’t happen, cells would be unable to make proteins and multiply. Nature has got round this problem by “engineering” special proteins that can change DNA’s shape, or “topology”, to get rid of the entanglements.
Dr Davide Michieletto, who is based in the School’s Institute for Condensed Matter and Complex Systems claims that DNA’s ability to morph its architecture means that it behaves a bit like soap:
The link between DNA and soap is certainly surprising. But by combining our knowledge of polymer physics and molecular biology, we can exploit this soapy feature to craft DNA-based soft materials that change topology over time. And by tweaking their topology, we can control their physical properties in unusual ways.
Soaps consists of “amphiphilic” molecules, one part of which loves water and another part that hates it. These molecules don’t exist in isolation but group together to form structures, known as “micelles”. At low concentrations, they are usually spherical, but at higher concentrations, the molecules can form long, tube-like structures, with the water-hating parts of the molecules facing inside.
These elongated, multi-molecule objects do strange things at high concentrations. In particular, just like DNA, they get entangled, increasing the fluid’s friction and making it harder to deform. In fact, the entanglements between worm-like micelles are what give soap, shampoo, face cream or hair gel that pleasant, smooth hand-feel.
Just like DNA, worm-like micelles can also disentangle themselves by constantly getting broken up and glued back together again with a new topology. But there’s one big difference: the DNA inside cells needs to preserve its genetic sequence otherwise cells might die or diseases could be triggered. In soap, there’s no precise sequence of monomers in micelles so they can be put back together in any order. This has a fundamental impact on how topological operations are performed on DNA: they have to happen at the right place and the right time.
To break DNA you need “restriction enzymes”, which cut the chain only where a certain DNA sequence is recognized. Topoisomerase proteins, meanwhile, have to be precisely positioned at certain locations on chromosomes where entanglements and mechanical stress often accumulate. Similarly, when two pieces of DNA reconnect and recombine – the process is tightly regulated in space and time to avoid aberrant chromosomes in cells. It’s almost as if DNA (thanks to proteins) behaved as a smart worm-like micelle.
Davide is definitely not the only person to see the potential of DNA as an advanced polymer, rather than just as genetic material. Over the last two decades, researchers have developed lots of new, DNA-based materials, such as hydrogels and nano-scaffolds, that could, for example, grow bones, tissues, skin and cells, using the unique properties of DNA to encode information.
What excites me about this line of research is that solutions of DNA, functionalized by the presence of proteins that can change DNA’s topology in time, may yield novel “topologically active” complex fluids that respond to external stimuli. For example, adding restriction enzymes that can cut the DNA at specific sequences could allow stiff and robust DNA-based scaffolds to be degraded as soon as they are no longer needed.
At the same time, adding topoisomerase to an ensemble of DNA plasmids (circular DNA) can create a gel, in which the rings of DNA are joined together like the rings on the logo of the modern-day Olympic Games. These “Olympic gels” have proved very difficult to synthesize chemically in the lab despite decades of trying, yet nature has been doing so for millions of years.
Apart from their intrinsic scientific interest, studying such biological structures will also help scientists design a new generation of self-assembled topological materials. These complex, DNA-based materials hold great technological promise, but to make progress, multidisciplinary teams of physicists, chemists and biologists are required.
We still need more top-quality journals that recognize high-value interdisciplinary research of this kind, while research centres that cut across traditional academic disciplines will be vital too. It is an exhilarating field to be in, where everyone – no matter where they are in their career – learns something new every day. My hope is that in 10 or 20 years’ time, scientists who are starting out in their careers will no longer feel obliged to explore only one specific discipline or to choose between theoretical and experimental work. Instead, it would be great if they could simply satisfy their scientific curiosity no matter what background they are from. For if they do that, who knows what we might find next?