Statistical Thermodynamics Approach for Intracellular Phase Separation
Statistical Thermodynamics Approach for Intracellular Phase Separation
复制标题
细胞内相分离的统计热力学方法
DOI：
10.1007/978-1-0716-2380-0_22
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发表时间：
2022
期刊：
影响因子：
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通讯作者：
Tomohiro Yamazaki
中科院分区：
文献类型：
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作者：
R. Tripathi;D. T. Adroja;C. Ritter;S. Sharma;C. Yang;A. D. Hiller;M. M. Koza;F. Demmel;A. Sundaresan;S. Langridge;W. Higemoto;T. U. Ito;A. M. Strydom;G. B. G. Stenning;A. Battacharyya;D. Keen;H. C. Walker;R. S. Perry;R. Pratt;Q. Si;T. ;Tokuro Shimokawa;Tomohiro Yamazaki
相分离是将活细胞中的生物分子区室化的基本过程之一。RNA-蛋白质复合物（RNP）通常通过相分离形成生物分子缩合物。我们在这里提出了一种统计热力学方法来研究细胞内相分离。我们首先介绍了两个分子（如蛋白质和溶剂分子）和聚合物溶液（如RNP和溶剂分子）的液-液相分离（LLPS）的统计热力学理论。由LLPS产生的冷凝物显示出粗化和/或聚结，以使其总表面积最小化。除了LLPS之外，还有其他类型的自组装，例如微相分离、胶束化、乳化和囊泡化，其中组装体的生长以最佳尺寸和形状停止。我们还描述了嵌段共聚物胶束的缩放理论，其中它们的结构类似于由NEAT1_2长非编码RNA（lncRNA）和RNA结合蛋白（RBP）的RNP支撑的paraspeckle核体的核-壳结构。这些理论处理聚合物在热力学平衡下的自组装，其中它们的浓度和组成不随时间变化。相反，RNP是根据RNA的转录产生的，并且随着时间的推移而降解。因此，我们考虑到动态方面的生产RNP的软物质的自组装理论的扩展。最后，我们讨论了paraspeckles的结构作为一个例子来证明，实验和理论相结合的方法是强大的研究细胞内相分离的机制。
Phase separation is one of the fundamental processes to compartmentalize biomolecules in living cells. RNA–protein complexes (RNPs) often scaffold biomolecular condensates formed through phase separation. We here present a statistical thermodynamics approach to investigate intracellular phase separation. We first present the statistical thermodynamic theory of the liquid-liquid phase separation (LLPS) of two molecules (such as proteins and solvent molecules) and of a polymer solution (such as RNPs and solvent molecules). Condensates produced by LLPS show coarsening and/or coalescence to minimize their total surface area. In addition to the LLPS, there are other types of self-assembly, such as microphase separation, micellization, emulsification, and vesiculation, with which the growth of the assembly stops with optimal size and shape. We also describe a scaling theory of micelles of block copolymers, where their structures are analogous to the core-shell structure of paraspeckle nuclear bodies scaffolded by RNPs of NEAT1_2 long noncoding RNAs (lncRNAs) and RNA-binding proteins (RBPs). These theories treat the self-assembly of polymers in the thermodynamic equilibrium, where their concentrations and compositions do not change with time. In contrast, RNPs are produced according to the transcription of RNAs and are degraded with time. We therefore take into account the dynamical aspect of the production of RNPs in an extension of the theory of the self-assembly of soft matter. Finally, we discuss the structure of paraspeckles as an example to demonstrate that an approach combining experiment and theory is powerful to investigate the mechanism of intracellular phase separation.