SELECTIVE ASSEMBLY, PHASE TRANSITIONS AND MOLECULAR KINETICS OF DNA OLIGOMERS.

In the last few years it has been shown that the spontaneous self-assembly process of short DNA and RNA duplexes into liquid crystal ordering is a likely potential route that led to the formation of first nucleic acids able to support biological activities. In particular, it has been experimentally demonstrated that liquid crystal domains behave as suitable micro-reactors to trigger polymerization between the stacked and not initially chemically linked short nucleic acids. Even paired mononucleotides at high enough concentration exhibit liquid crystal ordering, unveiling the crucial role of Watson-Crick selectivity and stacking attractive interactions among base pairs. In such a possible prebiotic context, DNA sequences with both random nucleobases sequence and length are likely to be formed. Surprisingly, it has been shown that even random DNA sequence of fixed length can support liquid crystal ordering at high concentration. The aim of this PhD thesis is to extend the knowledge of DNA liquid crystals self-assembly in the following four directions. First, I explored the selectivity of interaction in nucleic acids solutions of random-sequence DNA oligomers of different length L. The combination of experimental results and a suitable developed theoretical model revealed a not negligible percentage of perfect duplexes. Second, I investigated the process that leads to the onset of the nematic liquid crystal phase in aqueous solutions of DNA duplexes. The combination of static light scattering experiments and computer simulations made possible the study of both aggregation and local ordering of DNA duplexes in the isotropic phase, where no positional order is developed, and in proximity of the isotropic-nematic phase boundary. This study gives an insight of the role on the development of local orientational order among DNA duplexes both far and in proximity of the isotropic-nematic phase boundary. Third, I studied the diffusion of short DNA duplexes with attractive and repulsive interactions in the isotropic phase as a function of temperature. I found that the temperature dependence of diffusion coefficients reflects via an Arrhenius law the interduplex attractive interactions, whereas diffusion of repulsive duplexes is partially well described in terms of repulsive hard spheres. Fourth, I investigated phase diagrams of mixtures of DNA single strands and duplexes with various polycations that show liquid-liquid phase separations. This phenomena leads to the onset of a concentrated but still liquid phase of polyelectrolytes, called coacervate, in a bulk phase where polyelectrolytes are diluted. The most surprising result I found, it is the insurgence of liquid crystals in coacervates with 12 nucleobases long random DNA oligomers and polylysine at different ionic strengths. I believe that this PhD thesis adds important pieces to the self-assembly of nucleic acids puzzle, and in particular it shows how randomness of nucleic acids is not an impasse to both hybridization of defectless duplexes and liquid crystal ordering.