DNA-based material with tunable properties

Scientists have started to harness the properties of DNA to craft ‘topologically tunable’ complex fluids and soft materials, with potential applications in drug delivery and tissue regeneration.

DNA is a highly sophisticated polymer, and beyond the fact that it can store information, further fascinating aspects are its geometric and topological properties, such as knotting and supercoiling, very much like a twisted telephone cord. Through an international collaboration, scientists from the Universities of Edinburgh, San Diego and Vienna have started to harness these properties to craft ‘topologically tunable’ DNA-based complex fluids and soft materials.

The double helical shape of DNA has implications on its behaviour. A linear DNA molecule, that is a DNA molecule with two ends, can freely twist and turn. By contrast, joining the two ends to form a DNA circle entails that any over or under twisting of the double-helix remains ‘topologically locked’ i.e. the extra twist cannot be removed without cutting the molecule. Over or under twists have consequences for how DNA molecules arrange in space — in particular, they coil and buckle onto themselves very much like an old telephone cord into so called “supercoiled” conformations. The buckling of DNA relieves stress from the twisting, and thereby decreases the overall size of the molecule. For this reason it is thought that supercoiling is a natural mechanism employed by cells to package their genome into tiny spaces. While the smaller size naturally leads to faster movement of DNA molecules because of the lower drag, this behaviour does not occur when many DNA molecules are packed and entangled like spaghetti in a bowl.

The team of scientists performed large-scale computer simulations of dense and entangled solutions of DNA molecules with different degrees of supercoiling and found several surprising results. First, they discovered that the more supercoiled the DNA rings, the larger their size. Since the molecules needed to avoid each other, their shapes adopted strongly asymmetric and branched conformations that occupied more volume than their non-supercoiled counterparts. Intriguingly, the larger DNA molecules still displayed faster movement, which meant that the fluid of supercoiled DNA molecules had lower viscosity.

Supercoiled DNA molecules occurring naturally in bacteria are known as plasmids. In vivo, cells have special proteins called topoisomerase that can reduce the amount of supercoiling in plasmids. The team were able to use these proteins to control the extent of supercoiling in entangled DNA plasmids and studied their dynamics using fluorescent dyes. They discovered that DNA plasmids that were treated with topoisomerase, and hence with low supercoiling, were slower than their highly supercoiled counterparts.

To explain their findings, the team ran months-long simulations on powerful supercomputers which would have taken 228 years to run on a normal laptop and quantified how entangled the molecules in solutions were. While it is known that a ring-shaped polymer (similar to a circular DNA plasmid treated with topoisomerase) can be threaded by another ring, it was not known how this type of entanglement impacts the motion of supercoiled DNA. They found that a high degree of supercoiling decreases the penetrable area of each molecule resulting, in turn, in fewer threadings between the plasmids and ultimately yielding a fluid with lower viscosity. Nevertheless, the plasmids could still wrap around one another and constrain each others’ motion without threading. Yet, the supercoiling stiffens the conformations and thereby making them less prone to bend and entwine tightly, which reduces this type of entanglement too.

Davide Michieletto, one of the scientists involved in the project, who is based in the School's Institute for Condensed Matter and Complex Systems, concludes:

Not only did we find these novel effects in simulations, but we also demonstrated these trends experimentally and developed a theory describing them quantitatively. By changing the supercoiling we can tune the viscosity of these complex fluids at will. We now understand much better the connection between the adaptive geometry of the molecules and the resulting material properties. This is not only exciting from the fundamental perspective, but also promises useful applications. Using dedicated enzymes, such as the topoisomerase, one can design switchable DNA-based soft materials with tunable properties.