Stimuli-Responsive Synthetic Coacervates: Structural Design, Dynamics, and Functions

Abstract Liquid–liquid phase separation (LLPS), an interesting process in which a homogeneous solution demixes into solute-rich and solute-poor phases, serves as a ubiquitous mechanism for the formation of biomolecular condensates in living cells. Biomolecular condensates, also known as membraneless organelles, play critical roles in many fundamental physiological processes, including gene transcription, signal transduction, and stress responses. The intriguing LLPS phenomenon has inspired the development of artificial coacervates composed of biopolymers, synthetic macromolecules, or small molecules, driving exploration toward smart functional materials. For these synthetic coacervates, tailoring their structures and manipulating phase separation behaviors through external stimuli are essential to achieve precise functional control. This review summarizes recent advances in stimuli-responsive LLPS-based coacervates, focusing on structural design, formation mechanisms, stimuli-responsive characteristics, and functional applications. We thoroughly categorize the coacervates based on the diversity of stimulus sources used to regulate phase separation, with particular emphasis on the underlying molecular-level mechanisms. We highlight the applications of stimuli-responsive coacervates ranging from drug delivery and microreactors to biosensing. The prospects for stimuli-responsive LLPS systems for next-generation smart materials are also presented, aiming to elucidate their great potential in bridging the gap between the sophistication of biological coacervates and the performance of artificial smart materials.