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Macromolecular crowding as a cell volume sensor

机译:大分子拥挤作为细胞体积传感器

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The non-ideal properties of solutions containing high concentrations of macromolecules can result in enormous increases in the activity of the individual macromolecules. There is considerable evidence that macromolecular crowding and confinement not only occur in cells, but that these are major determinants of the activity of the proteins and other intracellular macromolecules. This concept has important implications for cell volume regulation because, under crowded conditions, relatively small changes in concentration, consequent to alterations of water content, lead to large changes in macromolecular activity which could provide a mechanism by which cells sense changes in their volume. This brief review considers 1) direct demonstrations that introducing a high concentration of appropriate macromolecules into cells in vitro produced volume regulatory changes, 2) the physical chemical principles involved in the effects of crowding of macromolecules on their activity, 3) estimates of the actual intracellular activity of macromolecules, 4) a proposed model of how changes in macromolecular crowding could signal volume regulation in cells, and 5) brief consideration of the complexities introduced by interactions between macromolecules, water and cosolutes. Conclusions: The hypothesis that macromolecular crowding provides a mechanism by which cells sense changes in their volume is plausible and is supported by striking observations in red blood cell ghosts and perfused barnacle muscle cells. However, the signaling molecules involved have not been identified, the proposed model is not fully consistent with the experiments, experimental verification in intact cells is lacking, and numerous alternative or additional mechanisms are not excluded. Copyright (C) 2000 S. Karger AG, Basel. [References: 19]
机译:包含高浓度大分子溶液的非理想特性可能会导致单个大分子活性的大幅增加。有大量证据表明大分子的拥挤和限制不仅发生在细胞中,而且这些是蛋白质和其他细胞内大分子活性的主要决定因素。该概念对细胞体积调节具有重要意义,因为在拥挤的条件下,由于水含量的变化,浓度变化相对较小,导致大分子活性发生较大变化,这可能提供了一种细胞感知其体积变化的机制。本文简要回顾了以下内容:1)直接证明,在体外向细胞中引入高浓度的适当大分子会产生体积调节变化; 2)涉及大分子拥挤对其活性影响的物理化学原理; 3)实际细胞内估计大分子的活性; 4)提出的大分子拥挤变化如何信号化细胞体积调节的模型,以及5)简要考虑大分子,水和溶质之间的相互作用所引入的复杂性。结论:大分子拥挤提供了一种机制,使细胞感知其体积变化的假说是合理的,并得到了对红细胞幽灵和灌注的藤壶肌细胞的惊人观察的支持。但是,尚未确定所涉及的信号分子,提出的模型与实验不完全一致,缺乏在完整细胞中进行实验验证,并且没有排除许多替代或其他机制。版权所有(C)2000 S.Karger AG,巴塞尔。 [参考:19]

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