Liquid Crystal Ordering of Random DNA Oligomers

Concentrated aqueous solutions of duplex-forming DNA ultra-short oligomers (6 to 20 base pairs) organize into various mesophases including the chiral nematic (NEM) and the columnar (COL) LC phases [1]. When the oligomer duplexes are mixed with single strands, LC phase formation proceeds through macroscopic phase separation in which double and single strands demix into LC domains and isotropic liquid [2]. Such behavior follows from the combination of various self-assembly processes including strand pairing, reversible linear aggregation, demixing and LC ordering. Here we extend our investigation to the case of LC ordering in oligonucleotides whose sequences are partially or entirely randomly chosen, i.e. in which, at given positions, the 4 primary nucleobases are found with equal probability. We have determined the phase diagram in the extended thermodynamic space that includes the degree of randomness R (left panel of the figure, N is sequence length). LC phases are observed in various random sequences. The extreme case is given by the COL phase found for entirely random 20mers, corresponding to a family of 420 ∼ 1012 different sequences (a micrograph through crossed polars is shown in the right panel of the figure). Through combined observations and simulations, we track the origin of this behavior. Random sequences pair into generally defected duplexes, a large fraction of them terminating with stretches of unpaired bases (overhangs). Overhangs promote linear aggregation of duplexes, with a mean strength depending on the overhang length. LC formation is accompanied by a phase separation where the duplexes with longer overhangs aggregate in columns and form COL LC domains that coexist with an isotropic fluid rich in duplexes whose structure impair them to aggregate.