Mixing protocols determine liquid–liquid phase separation dynamics in polyelectrolyte complex coacervation

Polyelectrolyte complex coacervation underpins many critical biological processes, yet how different initial mixing protocols determine its liquid-liquid phase separation (LLPS) dynamics remains unclear. Using molecular dynamics simulations, we show that when polycations and polyanions are initially randomly mixed, coacervate domain growth exhibits transient t1/2 scaling, driven by polymer network formation. This phase is followed by either t1 scaling due to hydrodynamic pumping or t1/3 scaling from droplet coarsening, depending on the initial mixing degree. Conversely, starting with spatially separated domains of polycations and polyanions-mimicking LLPS in certain marine organisms-leads to rapid coacervate formation, with early-stage growth following distinct t2/3 scaling due to strong electrostatic attraction, followed by continued growth via polymer accumulation. Both protocols yield significantly faster dynamics than systems initialized with preformed polyion pairs, which exhibit classical t1/3 scaling characteristic of droplet coarsening. These findings highlight the profound impact of initial conditions on LLPS dynamics in polyelectrolyte systems. Liquid-liquid phase separation is a process of interest, but the dynamics are still not fully understood. Here, the authors use molecular dynamics to consider the role of mixing protocol in polyelectrolyte complex coacervation.