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.

真核细胞的标志是包含基因组的细胞核，被称为核膜 (NE) 的物理屏障包围。一方面，这种划分赋予了真核细胞高度的调控复杂性和灵活性。另一方面，它提出了一个巨大的逻辑和能量问题，即每秒将数百万个分子运输穿过核膜，以促进它们在细胞所有隔室中的生物学功能。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”。

NPCs嵌入核膜中，控制和调节细胞核和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鲁棒性。值得注意的是，NPC 转运的功能机制在真核生物中高度保守，从酵母到人类，尽管不同物种之间的分子成分存在显着差异。

NPC是细胞中最大的大分子复合物。然而，尽管它非常复杂，但很明显，它的操作原理可以在很大程度上基于基本的物理概念来理解，正如从分子细胞生物学、生物物理学、纳米科学以及理论和计算建模的实验方法的组合中出现的那样。事实上，NPC 功能的许多方面都可以在人工模拟中重现，与生物孔隙相比，其复杂性大大降低。

我们回顾了当前对 NPC 结构和功能的物理理解，重点是通过理论和计算模型的镜头对细胞和人工 NPC 模拟物的实验研究进行批判性分析。我们还讨论了 NPC 操作的新兴概念与生物物理学和生物纳米技术的其他领域之间的联系。