Lee Daniel S W, Choi Chang-Hyun, Sanders David W, Beckers Lien, Riback Joshua A, Brangwynne Clifford P, Wingreen Ned S
Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ USA.
Present Address: Department of Bioengineering, University of California, Berkeley, CA USA.
Nat Phys. 2023;19(4):586-596. doi: 10.1038/s41567-022-01917-0. Epub 2023 Feb 2.
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.
生物分子相分离形成凝聚物已成为细胞内组织的一种机制，并影响许多细胞内过程，包括通过酶和途径中间体的聚集形成反应途径。凝聚物对反应进行精确而快速的时空控制需要调节其大小。然而，控制凝聚物大小分布的物理过程仍不清楚。在这里，我们表明天然和合成凝聚物均呈现指数大小分布，这可通过快速成核随后合并的蒙特卡洛模拟来捕捉。相比之下，病理性聚集体呈现幂律大小分布。这些不同的行为反映了成核和合并动力学的相对重要性。我们通过结合使用合成和天然凝聚物来探究决定凝聚物大小的潜在物理机制，从而证明了这一点。突然成核时指数分布的出现与连续成核时幂律分布的出现可能反映了一个决定凝聚物大小分布的普遍原则。
