(397d) Oligonucleotide – Peptide Complexes: Phase Control By DNA Hybridization

Understanding the interactions of charged polymers is one of the key problems in polymer physics, and is intimately related to the classic biophysics problem of DNA condensation by basic proteins and small cations. This study presents results of complexation of single- and double-stranded oligonucleotides (10 â?? 100 nt) by cationic peptides and polyamines, bridging the gap between â??shortâ? and â??longâ? polyelectrolytes. We observe several interesting behaviors, of which the most striking is that, while double-stranded oligonucleotides form solid precipitates when mixed with polycations, single-stranded oligonucleotides form liquid droplets (coacervates). Complexes are formed over a wide range of charge ratios, polymer lengths, and concentrations. When monovalent salt is added, precipitates formed by longer polymers â??meltâ?? into coacervates at a concentration that appears independent of polymer length, but the complexesâ?? (liquid and solid) stability vs dissolution is strongly dependent on length. Identical phase behavior is observed with RNA oligonucleotides, and when short polyamines are substituted for cationic peptides. Substitution of uncharged methyl phosphonate linkages indicates that polyelectrolyte charge density, rather than bending rigidity, determines the phase of the complexes. Single-stranded oligonucleotides remain competent for sequence-selective hybridization after coacervate formation, suggesting the possibility of environmentally-responsive complexes and nanoparticles for targeted therapeutic application or sensing.