Phase Behavior and Chain Conformation of Assoicative Guanidinium-Containing Polyelectrolytes in Aqueous Media

Liquid-liquid phase separation (LLPS) of biomolecular condensates is primarily driven by non-covalent associative interactions among specific sequences. Recently, the cationic arginine residue containing a guanidinium (G) group has emerged as a key dynamic binding motif for LLPS behavior in various proteins due to its unique ability to from a like-charge pairing, such as π–π interaction, in aqueous media when the electrostatic repulsion is reduced. In this study, a series of random copolyelectrolytes incorporating associative G (sticker) and non-associative ammonium (spacer) groups (G-ran-A) is employed with a various sticker fraction (0 ≤ f ≤ 1), while maintaining an overall positive charge. The phase behavior and chain conformation of G-ran-A in aqueous solutions were characterized as function of f, added salt concentration, and temperature. As f increases, the LLPS occurs at a lower C_salt and a lower temperature. Also, the radius of gyration (R_g) of G-ran-A chains decreases with increasing f. Our results indicates that the chain conformation and thus phase separation are precisely modulated by the associative sticker-sticker interaction and the fraction of stickers in a chain.