Modeling the Mechanisms by Which Coexisting Biomolecular RNA–Protein Condensates Form
Modeling the Mechanisms by Which Coexisting Biomolecular RNA–Protein Condensates Form
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共存生物分子 RNA-蛋白质凝聚物形成机制的建模
DOI：
10.1007/s11538-020-00823-x
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发表时间：
2020
影响因子：
3.5
通讯作者：
Newby, J. M.
中科院分区：
文献类型：
--
作者：
Gasior, K.;Forest, M. G.;Gladfelter, A. S.;Newby, J. M.
液-液相分离是细胞内组织的一种新兴机制。这项工作提出了一个数学模型来研究产生由不同RNA-蛋白质复合物组成的相分离液滴的分子机制。使用Cahn-Hilliard扩散界面模型与Flory-Huggins自由能方案，我们探讨如何多个（这里为简单起见，两个）蛋白质-RNA复合物（物种）可以建立一个异质液滴场，其中液滴与单一或多个物种相分离，并在粗化过程中发展。我们发现，复杂的复合物的去混合能量调谐是否复合物共存或形成不同的液滴，而瞬态结合动力学决定液滴形成的时间尺度和不同的物种相分离成液滴是否同时或顺序。对于特定的能量学和动力学，将出现仅由一种蛋白质-RNA复合物形成驱动的液滴场。慢慢地，其它液滴种类将在其它种类的预形成液滴内部积聚，从而允许它们占据相同的液滴空间。或者，不利的物种混合产生了寄生关系：缓慢形成的蛋白质-RNA复合物将积累在竞争性液滴物种的表面，当游离蛋白质释放时将其吸走。一旦这种竞争性蛋白质-RNA复合物在液滴表面上充分积累，它就可以形成新的液滴，该新的液滴能够与第一复合物液滴共享界面，但不能混合。这些结果提供了对广泛的相分离场景和共存但不混合在细胞的细胞核和细胞质内的异质液滴的见解。
Liquid–liquid phase separation is an emerging mechanism for intracellular organization. This work presents a mathematical model to examine molecular mechanisms that yield phase-separated droplets composed of different RNA–protein complexes. Using a Cahn–Hilliard diffuse interface model with a Flory–Huggins free energy scheme, we explore how multiple (here two, for simplicity) protein–RNA complexes (species) can establish a heterogeneous droplet field where droplets with single or multiple species phase separate and evolve during coarsening. We show that the complex–complex de-mixing energy tunes whether the complexes co-exist or form distinct droplets, while the transient binding kinetics dictate both the timescale of droplet formation and whether distinct species phase separate into droplets simultaneously or sequentially. For specific energetics and kinetics, a field of droplets driven by the formation of only one protein–RNA complex will emerge. Slowly, the other droplet species will accumulate inside the preformed droplets of the other species, allowing them to occupy the same droplet space. Alternatively, unfavorable species mixing creates a parasitic relationship: the slow-to-form protein–RNA complex will accumulateat the surfaceof a competing droplet species, siphoning off the free protein as it is released. Once this competing protein–RNA complex has sufficiently accumulated on the droplet surface, it can form a new droplet that is capable of sharing an interface with the first complex droplet but is not capable of mixing. These results give insights into a wide range of phase-separation scenarios and heterogeneous droplets that coexist but do not mix within the nucleus and the cytoplasm of cells.
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DOI：
10.1073/pnas.1504822112
发表时间：
2015-06-09
影响因子：
11.1
作者：
Elbaum-Garfinkle, Shana;Kim, Younghoon;Brangwynne, Clifford P.
通讯作者：
Brangwynne, Clifford P.
影响因子：
16
作者：
Lin Y;Protter DS;Rosen MK;Parker R
通讯作者：
Parker R
影响因子：
16
作者：
Pak CW;Kosno M;Holehouse AS;Padrick SB;Mittal A;Ali R;Yunus AA;Liu DR;Pappu RV;Rosen MK
通讯作者：
Rosen MK
瞬时交联动力学优化基因簇相互作用
影响因子：
4.3
作者：
Walker, Benjamin;Taylor, Dane;Lawrimore, Josh;Hult, Caitlin;Adalsteinsson, David;Bloom, Kerry;Forest, M. Gregory;Morozov, Alexandre V.
通讯作者：
Morozov, Alexandre V.
噬菌体中的朊病毒样结构域
影响因子：
5.2
作者：
G. Tetz;V. Tetz
通讯作者：
V. Tetz