Bioinspired programmable coacervate droplets and self-assembled fibers through pH regulation of monomers.

Phase separation and phase transitions pervade the biological domain, where proteins and RNA engage in liquid-liquid phase separation (LLPS), forming liquid-like membraneless organelles. The misregulation or dysfunction of these proteins culminates in the formation of solid aggregates via a liquid-to-solid transition, leading to pathogenic conditions. To decipher the underlying mechanisms, synthetic LLPS has been examined through complex coacervate formation from charged polymers. Nonetheless, temporal control over phase transitions from prebiotically relevant small organic synthons remains largely unexplored. Herein, we propose utilizing pH modulation to regulate the charge of small molecular building blocks, thereby controlling the LLPS process. Through a bio-inspired, enzyme-mediated pH-regulated reaction, we introduce temporal control over both LLPS and the transition from coacervates to supramolecular polymers. Additionally, by incorporating antagonistic pH modulators, we achieve transient LLPS and further temporal regulation of supramolecular polymer disassembly. Our investigation into pH-regulated LLPS provides a new avenue for exploring the stimuli-responsive, dynamic, and transient nature of LLPS.