Polyelectrolyte Complexes and Coacervates Formed by De Novo-Designed Peptides and Oligonucleotide

The liquid-liquid phase separation of biopolymers in living cells contains multiple interactions and occurs in a dynamic environment. Resolving the regulation mechanism is still a challenge. In this work, we designed a series of peptides (XXLY)6SSSGSS and studied their complexation and coacervation behavior with single-stranded oligonucleotides. The “X” and “Y” are varied to combine known amounts of charged and non-charged amino acids, together with the introduction of secondary structures and pH responsiveness. Results show that the electrostatic interaction, which is described as charge density, controls both the strength of complexation and the degree of chain relaxation, and thus determines the growth and size of the coacervates. The hydrophobic interaction is prominent when the charges are neutralized. Interestingly, the secondary structures of peptides exhibit profound effect on the morphology of the phases, such as solid phase to liquid phase transition. Our study gains insight into the phase separation under physiological conditions. It is also helpful to create coacervates with desirable structures and functions.