Buffering of biomolecular condensate volume and mass in multi-component mixtures.

Cells exhibit significant variations in the concentration of biomolecules, such as proteins and RNA, despite possessing identical genomes. These variations result from intrinsic fluctuations in the expression rates of proteins and RNA, as well as in the expression rates of molecules involved in transcription and translation, such as polymerases. Recently the formation of biomolecular condensates through liquid-liquid phase separation (LLPS) has been proposed as a powerful buffering mechanism to enable local protein concentration to be robust to noise. Here, using theory, simulations, in vitro and in vivo experiments we show orthogonal noise buffering mechanisms, whereby the total volume or mass of condensates is buffered when the global protein concentration changes. Our work provides new insights into the potential role of biomolecular condensates in functional biology.