Department of Physics and Astronomy, University of Padova, Padova, Italy.
Centre for Misfolding Diseases, Department of Chemistry, University of Cambridge, Cambridge, United Kingdom.
Elife. 2024 Nov 18;13:RP94214. doi: 10.7554/eLife.94214.
Many proteins have been recently shown to undergo a process of phase separation that leads to the formation of biomolecular condensates. Intriguingly, it has been observed that some of these proteins form dense droplets of sizeable dimensions already below the critical concentration, which is the concentration at which phase separation occurs. To understand this phenomenon, which is not readily compatible with classical nucleation theory, we investigated the properties of the droplet size distributions as a function of protein concentration. We found that these distributions can be described by a scale-invariant log-normal function with an average that increases progressively as the concentration approaches the critical concentration from below. The results of this scaling analysis suggest the existence of a universal behaviour independent of the sequences and structures of the proteins undergoing phase separation. While we refrain from proposing a theoretical model here, we suggest that any model of protein phase separation should predict the scaling exponents that we reported here from the fitting of experimental measurements of droplet size distributions. Furthermore, based on these observations, we show that it is possible to use the scale invariance to estimate the critical concentration for protein phase separation.
最近有许多研究表明，许多蛋白质会经历一个相分离的过程，导致生物分子凝聚物的形成。有趣的是，已经观察到这些蛋白质中的一些在低于相分离发生的临界浓度的情况下就形成了尺寸相当大的密集液滴。为了理解这一现象，它与经典成核理论不太兼容，我们研究了液滴尺寸分布随蛋白质浓度的变化特性。我们发现，这些分布可以用具有标度不变性的对数正态函数来描述，随着浓度从低于临界浓度逐渐接近临界浓度，平均值逐渐增加。这种标度分析的结果表明，存在一种与经历相分离的蛋白质的序列和结构无关的普遍行为。虽然我们在此不提出理论模型，但我们建议任何蛋白质相分离模型都应该根据液滴尺寸分布的实验测量拟合来预测我们这里报告的标度指数。此外，基于这些观察结果，我们表明可以利用这种标度不变性来估计蛋白质相分离的临界浓度。
