Photo by Dudzikr
Publish Date: 14.03.2022
Category: Interdisciplinary research, Our contribution to sustainable development goals
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Engineering materials for various bio-nanoapplications can profit from a robust self-assembly of DNA, e.g., the property that short DNA sequences (oligonucleotides) predominantly composed of guanine nucleobases, can self-assemble into extended nanostructures known as guanine wires or shortly G-wires. Their structural details and self-assembly mechanism are crucial for the optimization of G-wire’s properties; however, they are at present still quite poorly understood.
Researchers from the Faculty of Chemistry and Chemical Technology as well as the Faculty of Mathematics and Physics at the University of Ljubljana together with researchers from the National Institute of Chemistry (Slovenian NMR Centre and Department of Materials Chemistry), Jožef Stefan Institute (Department of Complex Matter), Faculty of Mechanical Engineering at the University of Maribor, Jožef Stefan International Postgraduate School, and the Center of Excellence EN-FIST have utilized nuclear magnetic resonance (NMR) to reveal how selected short, guanine-rich (G-rich) DNA oligonucleotides self-assemble into G-wires and thus obtained insights into behaviour of these nanostructures at the molecular level. Complementary methods, e.g., measurements of optical properties such as circular dichroism (CD), dynamic light scattering (DLS), and nanoscopic imaging methods, e.g., atomic force microscopy (AFM), scanning electron microscopy (SEM), and transmission electron microscopy (TEM), were used for further systematic characterization of the obtained G-wires. The crucial step of revealed sophisticated self-assembly mechanism includes a structural rearrangement of kinetically favoured G-quadruplex building block into a thermodynamically preferred one. G-quadruplexes are four stranded DNA structures that can be formed in G-rich regions of genomes. Unravelling details of this mechanism enabled the researchers to guide G-wire self-assembly in a controlled manner. They showed that properties of resulting G-wires, i.e., their length and thermal stability, can be tailored by changing the type and therefore, the features of loop residues. Molecular dynamics (MD) simulations provided insight into why loop residues with considerably different properties, i.e., hydrogen-bond affinity, stacking interactions, electronic effects, and hydrophobicity can induce an increase or a decrease of G-wire length.
Picture by Daša Pavc (National Institute of Chemistry)
The described discoveries will have important implications not only for further development of DNA nanotechnology, but also for deeper understanding of fundamental properties of G-quadruplex aggregates with biological significance. The work was published in prestigious scientific journal Nature Communications as a research article entitled ‘Understanding self-assembly at molecular level enables controlled design of DNA G-wires of different properties’ by the authors: Daša PAVC, Nerea SEBASTIAN, Lea SPINDLER, Irena DREVENŠEK-OLENIK, Gorazd KODERMAN PODBORŠEK, Janez PLAVEC and Primož ŠKET.