Vital intertwining

As tough as a medieval chainmail armour and as soft as a contact lens. This material is not taken from science fiction, it is a natural structure made of thousands of DNA circles interlinked with each other. Studying it can help us advance our knowledge in many fields, from biophysics and infectious diseases to materials science and biomedical engineering.

This topic is the subject of 'Organisation and dynamics of individual DNA segments in topologically complex genomes', an article that has been published in Nucleic Acid Research, the leading journal for the scientific community that studies DNA, RNA and genomes.

The study, which also appeared on the front cover of the journal, is the result of a collaboration between the Department of Physics of the University of Trento, with Guglielmo Grillo under the supervision of Luca Tubiana, and the Department of Physics and Astronomy of the University of Edinburgh, with Saminathan Ramakrishnan and Auro Varat Patnaik, supervised by Davide Michieletto.

The researchers focused on the structure and dynamics of kinetoplast DNA, the mitochondrial genome of Trypanosomes, with an experimental study led by Edinburgh and a computational analysis that involved simulations conducted by UniTrento. Trypanosomes are a family of parasites (flagellated protozoa) that pose a risk to humans and animals because they are responsible for a number of tropical diseases, such as leishmaniasis and sleeping sickness, which are transmitted by the bite of flies, mosquitoes or other insects.

Quantifying the spatial organization and dynamics of the different regions of the mitochondrial genome of this blood parasite is a major challenge in biology. And this particular genome stands out for characteristics that can be useful for the development of new materials.

"Trypanosomes are interesting single-celled eukaryotic organisms because their mitochondrial genome is made up of thousands of interlinked DNA rings, a kind of mesh chainmail on the micrometric scale. This 'Olympic network', reminiscent of the Olympic rings, is perfectly two-dimensional, and is crossed by some maxicircles that contain the genes essential for the production of energy in the parasite," says Tubiana, Professor of Biophysics at the University of Trento.

Tubiana describes the research work: "The Edinburgh team attached luminescent particles (quantum dots) to each of the 24 longest maxicircles, and was able to study not only their spatial distribution within the interlinked network of minicircles, but also their dynamics. We have seen that the maxicircles tend to be located at the periphery of the network and that they are characterized by very slow dynamics.

Through the simulations conducted in Trento, we then discovered not only that this peripheral location of the longer circles can contribute to the deformation of the structure, but also that the dynamics observed at the experimental level can be explained by assuming that the particles remain stuck in the microcircles, like fish in a net. Thanks to this discovery, we were able to use the information obtained from their motion to make an estimation of the elasticity of the entire structure.

Our method could be used more generally to quantify the spatial organization, dynamics, and material properties of other DNA structures.

A better understanding of the organization and dynamics of kinetoplast DNA is important in the fight against certain tropical diseases (such as leishmaniasis and sleeping sickness) because the mitochondrial genome is vital for the parasite. Interfering with the kinetoplast DNA kills the parasite by depriving it of ATP.

Such 'kinetoplast DNA' structure is a natural example of an 'Olympic gel', a material formed by braided rings postulated in 1980s by Nobel Prize winner P-G de Gennes but never realised in the lab. In fact, “it is humbling and at the same time inspiring that such an elusive structure has been made and replicated in single-celled parasites for millions of years without us knowing” said Michieletto.

More investigations into the kinetoplast DNA will finally help materials scientists to realise artificial interlinked Olympic structures with unusual properties. For example, current measurements suggest that the kinetoplast DNA is both “ultrasoft” and tough, two properties that are typically not found in the same material, and that are the the focus of much research in physics of matter, chemistry and materials sciences. “What we have observed in the study on the mechanical and elastic properties of kinetoplast DNA can therefore help us design materials with novel and uncommon properties and that can find applications as biomedical and bioelectronic devices," Tubiana concludes.