Protein Transport by the Nuclear Pore Complex: Simple Biophysics of a Complex Biomachine

In eukaryotic cells, transport of molecules between the nucleus and the cytoplasm is facilitated by highly selective and efficient biomachines known as nuclear pore complexes (NPCs). The structural details of NPCs vary across species, with many of their constituent proteins exhibiting relatively low sequence conservation; yet the NPC as a whole retains its general architecture and mechanism of action in all eukaryotes from yeast to humans. This functional conservation in the absence of precise molecular conservation suggests that many aspects of the NPC transport mechanism may be understood based on general biophysical considerations. Accordingly, some aspects of NPC function have been recapitulated in artificial nanochannel mimics, even though they lack certain molecular elements of the endogenous NPC. Herein, we review biophysical aspects of NPC architecture and function and cover recent progress in the field. We also review recent advances in man-made molecular filters inspired by NPCs, and their applications in nanotechnology. We conclude the review with an outlook on outstanding questions in the field and biomedical aspects of NPC transport.