Martin A. Fisher School of Physics, Brandeis University, Waltham, Massachusetts, United States of America.
PLoS Comput Biol. 2023 May 15;19(5):e1010652. doi: 10.1371/journal.pcbi.1010652. eCollection 2023 May.
Liquid condensate droplets with distinct compositions of proteins and nucleic acids are widespread in biological cells. While it is known that such droplets, or compartments, can regulate irreversible protein aggregation, their effect on reversible self-assembly remains largely unexplored. In this article, we use kinetic theory and solution thermodynamics to investigate the effect of liquid-liquid phase separation on the reversible self-assembly of structures with well-defined sizes and architectures. We find that, when assembling subunits preferentially partition into liquid compartments, robustness against kinetic traps and maximum achievable assembly rates can be significantly increased. In particular, both the range of solution conditions leading to productive assembly and the corresponding assembly rates can increase by orders of magnitude. We analyze the rate equation predictions using simple scaling estimates to identify effects of liquid-liquid phase separation as a function of relevant control parameters. These results may elucidate self-assembly processes that underlie normal cellular functions or pathogenesis, and suggest strategies for designing efficient bottom-up assembly for nanomaterials applications.
在生物细胞中广泛存在具有独特蛋白质和核酸组成的液态冷凝液滴。虽然人们已经知道，这些液滴或隔室可以调节不可逆的蛋白质聚集，但它们对可逆自组装的影响在很大程度上仍未得到探索。在本文中，我们使用动力学理论和溶液热力学来研究液-液相分离对具有明确定义大小和结构的结构的可逆自组装的影响。我们发现，当组装亚基优先分配到液态隔室时，对动力学陷阱的稳健性和最大可达组装速率可以显著提高。特别是，导致生产性组装的溶液条件范围以及相应的组装速率可以增加几个数量级。我们使用简单的缩放估计来分析速率方程预测，以确定液-液相分离作为相关控制参数函数的影响。这些结果可能阐明了正常细胞功能或发病机制下的自组装过程，并为设计用于纳米材料应用的高效自下而上组装的策略提供了思路。
