Composition can buffer protein dynamics within liquid-like condensates

Most non-membrane-bound compartments in cells that form via phase separation have complex composition. Phase separation of individual proteins that form these compartments has been well documented. However, we know relatively little about how the dynamics of individual proteins are modulated in multicomponent systems. Here, we used in vitro reconstitution and in vivo experiments to investigate how complex composition within a liquid-like ‘P granule’ compartment affects the dynamics of one of its scaffold proteins PGL-3. Using mutational analysis and biophysical perturbations, we generated PGL-3 constructs with reduced alpha-helicity that phase separate in vitro into condensates with widely varying dynamics. We use these PGL-3 constructs to show that introducing other P granule components buffers against large change of dynamics within liquid-like compartments. This dynamics-buffering effect is mediated by weak interactions among two or more components. Such dynamics-buffering may contribute to robust functional output of cellular liquid-like compartments.