Size distributions of intracellular condensates reflect competition between coalescence and nucleation

• Published in: Nature physics 2023, Vol.19 (4), p.586-596
• Main Authors: Lee, Daniel S. W., Choi, Chang-Hyun, Sanders, David W., Beckers, Lien, Riback, Joshua A., Brangwynne, Clifford P., Wingreen, Ned S.
• Format: Article
• Language: English
• Subjects: 631/57; 639/301/923/966; Atomic; Bioengineering; Biomolecules; Classical and Continuum Physics; Clustering; Coalescence; Complex Systems; Condensates; Condensed Matter Physics; Enzymes; Mathematical and Computational Physics; Molecular; Monte Carlo simulation; Nucleation; Optical and Plasma Physics; Phase separation; Physics; Physics and Astronomy; Physiology; Power law; Proteins; Simulation; Size distribution; Theoretical
• ISSN: 1745-2473; 1745-2481
• DOI: 10.1038/s41567-022-01917-0

Phase separation of biomolecules into condensates has emerged as a mechanism for intracellular organization and affects many intracellular processes, including reaction pathways through the clustering of enzymes and pathway intermediates. Precise and rapid spatiotemporal control of reactions by condensates requires tuning of their sizes. However, the physical processes that govern the distribution of condensate sizes remain unclear. Here we show that both native and synthetic condensates display an exponential size distribution, which is captured by Monte Carlo simulations of fast nucleation followed by coalescence. In contrast, pathological aggregates exhibit a power-law size distribution. These distinct behaviours reflect the relative importance of nucleation and coalescence kinetics. We demonstrate this by utilizing a combination of synthetic and native condensates to probe the underlying physical mechanisms determining condensate size. The appearance of exponential distributions for abrupt nucleation versus power-law distributions under continuous nucleation may reflect a general principle that determines condensate size distributions. Biomolecular condensates play a role in cellular processes and their size affects reaction pathways. The size distribution is connected to varying contributions of nucleation and coalescence.