Concentration buffering and noise reduction in non-equilibrium phase-separating systems

Biomolecular condensates have been proposed to buffer intracellular concentrations and reduce noise. However, concentrations need not be buffered in multicomponent systems, leading to a non-constant saturation concentration (c_sat) when individual components are varied. Simplified equilibrium considerations suggest that noise reduction might be closely related to concentration buffering and that a fixed saturation concentration is required for noise reduction to be effective. Here, we present a theoretical analysis to demonstrate that these suggestions do not apply to mesoscopic fluctuating systems. We show that concentration buffering and noise reduction are distinct concepts, which cannot be used interchangeably. We further demonstrate that concentration buffering and a constant c_sat are neither necessary nor sufficient for noise reduction to be effective. Clarity about these concepts is important for studying the role of condensates in controlling cellular noise and for the interpretation of concentration relationships in cells. A record of this paper's transparent peer review process is included in the supplemental information.