Self-oscillating coacervates: an internal chemical clock sustains membraneless protocell populations

Living systems establish temporal order in molecular processes while operating far from thermodynamic equilibrium. This temporal control is implemented by internal clocks, which are biochemical networks that set the timing of biological processes ^1-3 . Clock-regulated mechanisms are essential for organizing the dynamics of living systems in time; however, a strategy to harness internal clocks as programmable regulators in synthetic life-like systems remain to be established ^4-6 . Here we show the implementation of an internal chemical clock into membraneless coacervate protocells, thereby bringing protocell populations into long-time existence against coarsening toward thermodynamic equilibrium. The clock periodically enforces time-limited alternation between the emergence, coalescence, and dissolution regimes in coacervate protocells, sustaining a periodic steady state far from equilibrium. When the clock is exhausted, regulation fails and uncontrolled coarsening resumes, underscoring the causal role of time-programmed control. Moreover, tuning the clock period shifts the average size of the coacervate protocells, indicating kinetic control by the clock’s period. We anticipate that this work will pave the way for future clock-regulated functions in artificial protocells.