Size Distributions of Intracellular Condensates Reflect Competition Between Coalescence and Nucleation

Authors

Daniel S W Lee
Chang-Hyun Choi
David W Sanders
Lien Beckers
Joshua A Riback
Clifford P Brangwynne
Ned S Wingreen

Publication Date

1-1-2023

Journal

Nature Physics

DOI

10.1038/s41567-022-01917-0

PMID

37073403

PMCID

PMC10104779

PubMedCentral® Posted Date

2-2-2023

PubMedCentral® Full Text Version

Post-Print

Published Open-Access

yes

Keywords

Biophysics, Self-assembly

Abstract

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.

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