Department of Chemical and Biological Physics, Weizmann Institute of Science, Rehovet 76100, Israel.
Proc Natl Acad Sci U S A. 2022 May 24;119(21):e2118301119. doi: 10.1073/pnas.2118301119. Epub 2022 May 17.
The volume of the cell nucleus varies across cell types and species and is commonly thought to be determined by the size of the genome and degree of chromatin compaction. However, this notion has been challenged over the years by much experimental evidence. Here, we consider the physical condition of mechanical force balance as a determining condition of the nuclear volume and use quantitative, order-of-magnitude analysis to estimate the forces from different sources of nuclear and cytoplasmic pressure. Our estimates suggest that the dominant pressure within the nucleus and cytoplasm of nonstriated muscle cells originates from the osmotic pressure of proteins and RNA molecules that are localized to the nucleus or cytoplasm by out-of-equilibrium, active nucleocytoplasmic transport rather than from chromatin or its associated ions. This motivates us to formulate a physical model for the ratio of the cell and nuclear volumes in which osmotic pressures of localized proteins determine the relative volumes. In accordance with unexplained observations that are a century old, our model predicts that the ratio of the cell and nuclear volumes is a constant, robust to a wide variety of biochemical and biophysical manipulations, and is changed only if gene expression or nucleocytoplasmic transport is modulated.
细胞核的体积在不同的细胞类型和物种中有所变化，通常被认为是由基因组的大小和染色质的紧凑程度决定的。然而，多年来，大量的实验证据对这一观点提出了挑战。在这里，我们将力学平衡的物理状态视为细胞核体积的决定条件，并使用定量的数量级分析来估计来自核和细胞质压力的不同来源的力。我们的估计表明，非横纹肌细胞的核和细胞质内的主要压力源自蛋白质和 RNA 分子的渗透压，这些蛋白质和 RNA 分子通过非平衡的、活跃的核质转运被定位到核或细胞质中，而不是来自染色质或其相关离子。这促使我们提出了一个物理模型，用于描述细胞和细胞核体积的比例，其中局部化蛋白质的渗透压决定了相对体积。根据一个世纪以来未得到解释的观察结果，我们的模型预测，细胞和细胞核体积的比例是一个常数，对各种生化和生物物理操作具有很强的稳健性，只有在基因表达或核质转运被调节时才会发生变化。
