Spontaneous self-assembly of nucleic acids: liquid crystal condensation of complementary sequences in mixtures of DNA and RNA oligomers 

“Le cose tutte quante hanno ordine tra loro, e questo e' forma che l'universo a Dio fa simigliante.” (Dante Alighieri, Divina Commedia, Paradiso, I, 103)

[All things whate'er they be Have order among themselves, and this is form, That makes the universe resemble God]

A remarkable example of spontaneous self-assembly of biomolecules, driven purely by physical interactions, is reported. Short, complementary DNA and RNA oligomers, down to six bases in length, exhibit lyotropic liquid crystal phases, chiral nematic and columnar, although these duplexes lack the shape anisotropy required for liquid crystal ordering. Such phases are produced by the end-to-end stacking of the duplex oligomers into polydisperse, anisotropic, rod-shaped aggregates, which can order into liquid crystals. Furthermore, when only a fraction of the sample is composed of complementary sequences, and hence the solution is effectively a mixture of single strands and double-stranded helices, the system is found to phase separate with duplex-rich liquid crystalline domains emerging from an isotropic background rich in single strands. This spontaneous partitioning, resulting from a combination of entropic and enthalpic factors, is sensitive to the degree of complementarity of the sequences and can be tuned with temperature. We suggest that in a chemical environment where oligomer ligation is possible, such ordering and condensation could provide a plausible route for the selective synthesis of extended complementary oligomers, a mechanism of possible relevance in prebiotic scenarios.