Jamming-free crowded transport through the nuclear pore complex*

The nuclear pore complex (NPC) is the main conduit for transporting materials into and out of the nucleus of eukaryotic cells. The central channel of the NPC is crowded with many simultaneously translocating cargoes. Crowding is known to slow down transport in many systems, requiring additional mechanisms to mitigate negative effects. Yet surprisingly, past experiments have shown that crowding can benefit cargo transport through the NPC, by increasing transport efficiency and decreasing transport time, thus avoiding jamming. We simulate an NPC mimic containing only the main components of the NPC system -- polymeric intrinsically disordered proteins (called FG nups) which line the NPC channel, and transport proteins which ferry cargoes across the FG nup assembly -- and their coarse-grained interactions with each other. We show that the regime of jamming-free transport is possible if (and only if) FG nups within the NPC are spatially arranged into “vestibule” and “barrier” regions, as previously suggested by experiments. Our analysis provides the first theoretical explanations for how crowding can benefit transport in the NPC, and suggests a functional reason for why the NPC internal spatial structure is evolutionarily conserved across species.