Research Center for Molecular Mechanisms of Aging and Age-Related Diseases, Moscow Institute of Physics and Technology, Institutskiy pereulok, 9, Dolgoprudny 141700, Russia; Kurchatov Complex of NBICS-Technologies, National Research Center Kurchatov Institute, Moscow 123182, Russia.
Research Center for Molecular Mechanisms of Aging and Age-Related Diseases, Moscow Institute of Physics and Technology, Institutskiy pereulok, 9, Dolgoprudny 141700, Russia.
Biochim Biophys Acta Mol Cell Res. 2021 Oct;1868(11):119102. doi: 10.1016/j.bbamcr.2021.119102. Epub 2021 Jul 20.
This work is devoted to the phenomenon of liquid-liquid phase separation (LLPS), which has come to be recognized as fundamental organizing principle of living cells. We distinguish separation processes with different dimensions. Well-known 3D-condensation occurs in aqueous solution and leads to membraneless organelle (MLOs) formation. 2D-films may be formed near membrane surfaces and lateral phase separation (membrane rafts) occurs within the membranes themselves. LLPS may also occur on 1D structures like DNA and the cyto- and nucleoskeleton. Phase separation provides efficient transport and sorting of proteins and metabolites, accelerates the assembly of metabolic and signaling complexes, and mediates stress responses. In this work, we propose a model in which the processes of polymerization (1D structures), phase separation in membranes (2D structures), and LLPS in the volume (3D structures) influence each other. Disordered proteins and whole condensates may provide membrane raft separation or polymerization of specific proteins. On the other hand, 1D and 2D structures with special composition or embedded IDRs can nucleate condensates. We hypothesized that environmental change may trigger a LLPS which can propagate within the cell interior moving along the cytoskeleton or as an autowave. New phase propagation quickly and using a low amount of energy adjusts cell signaling and metabolic systems to new demands. Cumulatively, the interconnected phase separation phenomena in different dimensions represent a previously unexplored system of intracellular communication and regulation which cannot be ignored when considering both physiological and pathological cell processes.
这项工作致力于研究液-液相分离（LLPS）现象，该现象已被认为是活细胞的基本组织原则。我们区分了不同维度的分离过程。众所周知的 3D 凝聚发生在水溶液中，导致无膜细胞器（MLOs）的形成。2D 膜附近可能形成薄膜，而膜本身内部则发生侧向相分离（膜筏）。LLPS 也可能发生在 DNA 和细胞质和核骨架等 1D 结构上。相分离可有效运输和分拣蛋白质和代谢物，加速代谢和信号复合物的组装，并介导应激反应。在这项工作中，我们提出了一个模型，其中聚合（1D 结构）、膜中的相分离（2D 结构）和体积中的 LLPS（3D 结构）相互影响。无序蛋白质和整个凝聚物可能提供膜筏分离或特定蛋白质的聚合。另一方面，具有特殊组成或嵌入 IDR 的 1D 和 2D 结构可以引发凝聚。我们假设环境变化可能引发 LLPS，该过程可以沿着细胞骨架在内质内传播，或者作为自动波传播。新的相传播迅速，只需消耗少量能量即可调节细胞信号转导和代谢系统以满足新需求。总之，不同维度的相互关联的相分离现象代表了一种以前未被探索的细胞内通讯和调节系统，在考虑生理和病理细胞过程时不容忽视。
