A model of diffusion through a potential captures the effect of competition on the efficiency and speed of nucleocytoplasmic transport

The nuclear pore complex (NPC) facilitates the selective transport of materials between the nucleus and cytoplasm in eukaryotic cells. Typically, many cargo are simultaneously present within the NPC during transport, and it is not fully understood how the NPC can function efficiently despite the crowding in the channel. In this study, we simulate transport through an NPC-like channel with coarse-grained cargoes and NPC-associated intrinsically disordered proteins (FG nucleoporins). From the results of this simulation, we show that cargo densities and trajectories along the direction of transport can be captured by a model of 1-dimensional diffusion through a potential, which is an effective potential arising through the interactions between cargoes and NPC components, and is modified by the non-equilibrium density profiles of cargoes inside the channel. With this framework, we are able to account qualitatively for previously unexplained experimental data which show that an increased number of cargo results in both increased efficiency and speed of transport. Our model therefore provides an explanation for why crowding does not necessarily affect the functioning of the NPC in a negative way, which can explain how the NPC can achieve both high specificity and high throughput.