Salt-Bridge-Mediated Coacervate-to-Vesicle Transformation in Arginine-Rich Coacervates

Polypeptide-based liquid-liquid phase separation (LLPS) has received considerable attention as it governs the formation of membraneless organelles in cells. However, the detailed mechanistic understanding of how one of the most prevalent cationic amino acids in proteins, arginine, interacts with various biomolecules to induce phase separation and undergo morphogenesis remains to be resolved. Herein, we report the phase separation behavior and transformation of arginine-rich coacervates into vesicular structures upon introducing polyphosphates. Transformation into vesicles was shown to occur independent of the initial anionic counterparts and was driven by salt-bridge interactions between guanidinium groups of arginine residues and phosphates. We also investigate the role of intermolecular forces and ionic effects on the morphological transformation and further exploit their potential in the assembly of artificial tissue-like constructs. Overall, our findings underpin a unifying principle for vesicle transformation from arginine-rich coacervates and their potency for reconstituting hierarchical biological microcompartments.