Hoogenboom Bart W, Hough Loren E, Lemke Edward A, Lim Roderick Y H, Onck Patrick R, Zilman Anton
London Centre for Nanotechnology and Department of Physics and Astronomy, University College London, London WC1E 6BT, United Kingdom.
Department of Physics and BioFrontiers Institute, University of Colorado, Boulder CO 80309, United States of America.
Phys Rep. 2021 Jul 25;921:1-53. doi: 10.1016/j.physrep.2021.03.003. Epub 2021 Mar 24.
The hallmark of eukaryotic cells is the nucleus that contains the genome, enclosed by a physical barrier known as the nuclear envelope (NE). On the one hand, this compartmentalization endows the eukaryotic cells with high regulatory complexity and flexibility. On the other hand, it poses a tremendous logistic and energetic problem of transporting millions of molecules per second across the nuclear envelope, to facilitate their biological function in all compartments of the cell. Therefore, eukaryotes have evolved a molecular "nanomachine" known as the Nuclear Pore Complex (NPC). Embedded in the nuclear envelope, NPCs control and regulate all the bi-directional transport between the cell nucleus and the cytoplasm. NPCs combine high molecular specificity of transport with high throughput and speed, and are highly robust with respect to molecular noise and structural perturbations. Remarkably, the functional mechanisms of NPC transport are highly conserved among eukaryotes, from yeast to humans, despite significant differences in the molecular components among various species. The NPC is the largest macromolecular complex in the cell. Yet, despite its significant complexity, it has become clear that its principles of operation can be largely understood based on fundamental physical concepts, as have emerged from a combination of experimental methods of molecular cell biology, biophysics, nanoscience and theoretical and computational modeling. Indeed, many aspects of NPC function can be recapitulated in artificial mimics with a drastically reduced complexity compared to biological pores. We review the current physical understanding of the NPC architecture and function, with the focus on the critical analysis of experimental studies in cells and artificial NPC mimics through the lens of theoretical and computational models. We also discuss the connections between the emerging concepts of NPC operation and other areas of biophysics and bionanotechnology.
真核细胞的标志是含有基因组的细胞核，细胞核被称为核膜（NE）的物理屏障所包围。一方面，这种区室化赋予真核细胞高度的调控复杂性和灵活性。另一方面，它带来了一个巨大的后勤和能量问题，即每秒要将数百万个分子运输穿过核膜，以促进它们在细胞所有区室中的生物学功能。因此，真核生物进化出了一种被称为核孔复合体（NPC）的分子“纳米机器”。NPC嵌入核膜中，控制和调节细胞核与细胞质之间的所有双向运输。NPC将运输的高分子特异性与高通量和速度相结合，并且在分子噪声和结构扰动方面具有高度的稳健性。值得注意的是，尽管不同物种之间的分子成分存在显著差异，但从酵母到人类，真核生物中NPC运输的功能机制高度保守。NPC是细胞中最大的大分子复合体。然而，尽管其极其复杂，但很明显，基于分子细胞生物学、生物物理学、纳米科学以及理论和计算建模等实验方法所产生的基本物理概念，其运作原理在很大程度上是可以理解的。事实上，与生物孔相比，人工模拟物的复杂性大幅降低，却能概括NPC功能的许多方面。我们回顾了目前对NPC结构和功能的物理学理解，重点是通过理论和计算模型的视角对细胞实验研究和人工NPC模拟物进行批判性分析。我们还讨论了NPC运作的新兴概念与生物物理学和生物纳米技术其他领域之间的联系。
