The role of model crowders in the salt resistance of complex coacervates

Complex coacervation is the phase separation of oppositely charged polyelectrolytes, resulting in a polymer-dense coacervate phase and a polymer-depleted supernatant phase. Coacervation is crucial for many biological processes and novel synthetic materials, where the environment is often filled with other neutral molecules (crowders). Yet, the complex role of crowders in complex coacervation has not been studied systematically under controlled conditions. We performed coarse-grained molecular dynamics simulations of coacervation in the presence of polymeric crowders of varying concentrations and chain lengths. While short crowders do not have any significant effect on coacervation, larger crowders stabilize the coacervate against added salt, increasing its critical salt concentration. The change in critical salt concentration saturates for long crowders at a value determined by the crowder concentration. Rescaling all phase diagrams by their critical salt concentration leads to a collapse of the data, which demonstrates a universal phase behavior. Our simulation indicates that the inability of crowder chains to mix with the polyelectrolytes is the driving force behind crowding effects. These testable predictions provide a first step toward a comprehensive understanding of crowding effects in complex coacervation.