Size Scaling of Condensates in Multicomponent Phase Separation

Constant proportionalities between cells and their intracellular organelles have been widely observed in various types of cells, known as intracellular size scaling. However, the mechanism underlying the size scaling and its modulation by environmental factors in multicomponent systems remain poorly understood. Here, we study the size scaling of membrane-less condensates using microdroplet-encapsulated minimalistic condensates formed by droplet microfluidics and mean-field theory. We demonstrate that the size scaling of condensates is an inherent characteristic of liquid-liquid phase separation. This concept is supported by experiments showing the occurrence of size scaling phenomena in various condensate systems and a generic lever rule acquired from mean-field theory. Moreover, it is found that the condensate-to-microdroplet scaling ratio can be affected by the solute and salt concentrations, with good agreement between experiments and predictions by theory. Notably, we identify a noise buffering mechanism whereby condensates composed of large macromolecules effectively maintain constant volumes and counteract concentration fluctuations of small molecules. This mechanism is achieved through the dynamic rearrangement of small molecules in and out of membrane-free interfaces. Our work provides crucial insights into understanding mechanistic principles that govern the size of cells and intracellular organelles as well as associated biological functions. © 2024 American Chemical Society.