Liquid Crystal Ordering and Isotropic Gelation in Solutions of Four-Base-Long DNA Oligomers

Abstract

Liquid crystal ordering is reported in aqueous solutions of the oligomer 5'-ATTAp-3' and of the oligomer 5'-GCCGp-3'. In both systems, we quantitatively interpret ordering as stemming from the chaining of molecules via a "running-bond" type of pairing, a self-assembly process distinct from the duplex aggregation previously reported for longer oligonucleotides. While concentrated solutions of 5'-ATTAp-3' show only a columnar liquid crystal phase, solutions of 5'-GCCGp-3' display a rich phase diagram, featuring a chiral nematic phase analogous to those observed in solutions of longer oligonucleotides and two unconventional phases, a columnar crystal and, at high concentration, an isotropic amorphous gel. The appearance of these phases, which can be interpreted on the basis of features of 5'-GCCGp-3'molecular structure, suggests distinctive assembly motifs specific to ultrashort oligonucleotides.

Understanding the origin of liquid crystal ordering of ultrashort double-stranded DNA

“…It is interesting to see that very small DNA fragments can give rise to columns sufficiently rigid to give rise to LC phase. Very recently, Fraccia et al [7] have demonstrated LC phase for such short DNA fragments which our study compliments. The repulsive sideby-side interaction of blunt-end DNA is mostly governed by electrostatic interactions.…”

“…That is, the SDSA-enabled liquid crystal order acts as a molecular selector, physically collecting sufficiently complementary and attractive oligomers. In the presence of appropriate abiotic ligation chemistry, the physical proximity and organization of reacting duplex end-groups, characteristic of the LC ordering, strongly accelerates ligation of duplex oligomers into longer polymers in the LC phase [6,7]. Since the LC ordering in turn becomes more stable as oligomer length increases, this ligation is effectively auto-catalytic, a step in a positive feedback loop, known as liquid crystal auto-catalysis (LCA) [6], that promotes LC ordering and oligomer lengthening.…”

“…LC ordering of duplex DNA has been reported for complementary oligomers as short as 6 bases, and LC autocatalysis has currently been demonstrated for oligomers as short as 12 bases [6,7]. An exciting challenge is to extend these observations to shorter oligomers and ultimately solutions of single bases, which then could be considered as models for the process that led to the appearance of sequence-directed self assembling polymers in the pre-biotic era [8].…”

Liquid Crystal Ordering of Four-Base-Long DNA Oligomers with Both G–C and A–T Pairing

“…[14], the main contribution to the stability of GCTA complexes comes from the interaction between the overhangs of two linear aggregates already composed by more than 3 strands. Such interaction involves either the formation of a GC/CG or of a TA/AT pair, having free energy ∆G GC and ∆G TA , respectively, as sketched in Figure 2C.…”

“…A step in this direction was the recent observation of LC phases and isotropic gelation in two different DNA sequences having lengths of only four bp: 5 -GCCG-3 P (GCCGp) and 5 -ATTA-3 P (ATTAp), which, despite their length, were found to form aggregates by the pairing of their GC and AT terminals, respectively [14]. Here we report an extension of that work with LC ordering found in concentrated aqueous solutions of DNA 4mers 5 -GCTA-3 sequence (GCTA), which can mutually interact by Watson-Crick pairing of either the 5 -terminal bases, GC/CG, or the 3 -terminal bases, TA/AT.…”