Sticker Valence Governs Chain Collapse and Liquid‐Liquid Phase Separation in Peptide‐Inspired Associative Polymers

Biomolecular condensates, including membraneless organelles, form through liquid-liquid phase separation (LLPS) driven by sequence-specific associations within intrinsically disordered protein regions. Understanding how sticker valence governs LLPS is essential for predicting pathological aggregation and designing programmable biomaterials. Among associative amino acid motifs, cationic arginine (Arg) is a key regulator of biological LLPS, yet the molecular basis of its distinct phase behavior remains incompletely understood. Here, we investigate peptide-inspired heteropolymers composed of associative Arg-like guanidinium stickers and lysine-like ammonium spacers. The interchain sticker-sticker associations lead to LLPS, and sticker valence governs the phase separation behavior. Prior to macroscopic phase separation, enhanced sticker associations induce a continuous coil-to-globule transition even under overall good-solvent conditions, thereby facilitating LLPS. At interfaces, elevated salt counterintuitively reduces inter-surface cohesion despite stronger sticker associations, because preferential intra-surface network formation depletes free stickers available for inter-surface binding; this cohesion can be transiently restored by mechanical stimulation. These results establish a molecular framework linking sticker valence, chain collapse, phase separation, and interfacial mechanics in associative polymers, and identify peptide-inspired sticker-spacer heteropolymers as a versatile platform for programmable condensates and responsive soft materials.