The Impact of Ionic Atmosphere, Polycation Chemistry, and Sequence Dependence on DNA Polyelectrolyte Complexation

When oppositely charged polymers are mixed in solution, they undergo phase separation and polyelectrolyte complexes (PECs) form. PECs containing nucleic acid (NA) polyanions exhibit distinct phase behavior compared to synthetic PECs due to the complex chemistry and secondary structure of NAs. The systematic characterization of the chemical and physical phase behavior of NA PECs is crucial to their use as highly programmable soft materials and therapeutic delivery systems. In this work, bright field microscopy and turbidity was used to visualize and quantify the phase behavior of these NA PECs and develop relationships to polymer selection and solution conditions. The PECs studied in this project explore 1) polycation chemistries differing in methylation, chirality and side chain chemistry, 2) NA sequence dependence, and 3) the ionic atmosphere. We show that ion selection of monovalent (KCl, NaCl, LiCl) and divalent (CaCl2, MgCl2) salts impacts the local molecular interactions with NAs, which impact PEC phase behavior. One ion effect of interest is the cation-pi interaction strength which could expose how specific salt ions influence PEC complexation and dissociation.