Exploiting the properties of DNA to manufacture “topologically tunable” DNA-based materials

Although DNA is often idealized as the “molecule of life,” it is also a highly sophisticated polymer that can be used for next-generation materials. Beyond the fact that it can store information, other fascinating aspects of DNA are its geometric and topological properties, such as knotting and supercoiling.

This is because just like a twisted telephone cord, DNA is often found coiled inside bacteria and other cells and even tied up in viruses.

Now, a collaboration of scientists from the Universities of Edinburgh, San Diego and Vienna have begun to exploit these properties to fabricate complex fluids and “topologically adjustable” DNA-based soft materials with potential applications in administration. drug and tissue regeneration, as published in Scientific progress.

The well-known shape of the DNA double helix has profound implications for its behavior. A linear DNA molecule, that is, a DNA molecule with two ends, can twist and spin freely. In contrast, joining the two ends to form a DNA circle implies that any twist on or under the double helix remains “topologically locked”, i.e. the extra twist cannot be removed without cutting. the molecule.

Twists above or below have interesting consequences for how DNA molecules organize themselves in space – in particular, they twist and loop on themselves just like an old telephone cord in so-called supercoiled conformations (Fig. 1). The DNA buckling relieves the stress of over / under torsion, and thus decreases the overall size of the molecule.

For this reason, it is believed that supercoiling is a natural mechanism that cells use to pack their genome into tiny spaces. While the smaller size naturally leads to faster diffusion of DNA molecules in solution, for example in water or through the pores of the gel, due to the lower drag, this well understood behavior does not occur. when many DNA molecules are wrapped and tangled like spaghetti in a bowl.

We performed large-scale computer simulations of dense solutions of DNA molecules with varying degrees of supercoiling and found several surprising results. Unlike the diluted case, the more supercoiled DNA rings, the larger their size. “

Jan Smrek, first author of the study, University of Vienna

Since molecules must avoid each other, their shapes adopt strongly asymmetric and branched conformations that occupy more volume than their non-supercoiled counterparts. Strangely enough, and contrary to expectations, “the larger molecules of DNA always produce faster diffusion”. The faster diffusion means that the solution has a lower viscosity.

The supercoiled DNA molecules found naturally in bacteria are called plasmids. In vivo, cells have special proteins called topoisomerase which can reduce the amount of supercoiling in plasmids. “Thanks to these proteins – which can be purified and used in the laboratory – we are able to monitor the extent of supercoiling in entangled DNA plasmids and study their dynamics using fluorescent dyes. We were amazed to find that indeed, DNA plasmids that have been treated with topoisomerase, and therefore with low supercoiling, are slower than their highly supercoiled counterparts. explains Rae Robertson Anderson, who led the experiments at the University of San Diego.

To explain the surprisingly faster dynamics, the scientists used large-scale simulations on supercomputers to quantify how much the molecules in solutions are entangled. Although it is known that a ring-shaped polymer – quite similar to a circular DNA plasmid – can be threaded through another ring, meaning that the latter can pierce the eye of the former, we do not didn’t know how this type of entanglement affects the movement of supercoiled DNA.

Through the simulations, the scientists found that a high degree of supercoiling decreases the penetrable area of ​​each molecule, which in turn results in fewer threads between the plasmids and ultimately results in a solution with a lower viscosity.

Nevertheless, the plasmids could still wrap around each other and constrain each other’s movements without threading. Yet overwinding stiffens conformations and thus makes them less likely to bend and entwine tightly, which also reduces this type of entanglement.

Davide Michieletto of the University of Edinburgh concludes, “Not only have we found these new effects in simulations, but we have also demonstrated these trends experimentally and developed a theory describing them quantitatively. By modifying the supercoiling, we can tune the viscosity of these complex fluids to We now understand much better the connection between the adaptive geometry of molecules and the resulting material properties. This is not only fundamentally exciting, but also promises useful applications. From dedicated enzymes, like topoisomerase, one can design flexible, switchable DNA-based materials with adjustable properties. “


Journal reference:

Smrek, J., et al. (2021) Topological adjustment of DNA mobility in entangled solutions of supercoiled plasmids. Scientific progress. doi.org/10.1126/sciadv.abf9260.

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