Nuclear pore complexes (NPCs) allow the selective exchange of molecules between the cytoplasm and cell
nucleus. Although small molecules can diffuse freely through a NPC, the transport of proteins and nucleotides
requires association with transport factors (kaps). The latter transiently bind to disordered flexible polymers
within the NPC, known collectively as phenylalanine-glycine-nucleoporins (FG-Nups). It has recently been
shown that transient binding combined with diffusion in the bound state is a sufficient mechanism for selective
transport. However, selectivity is significantly reduced if the mobility of the bound state is too slow. In this
paper we formulate the binding-diffusion mechanism of selective transport in terms of a “stochastically gated”
diffusion process in which each bound particle undergoes confined diffusion within a subdomain of the NPC.
This allows us to make explicit the fact that the diffusion of a particle when bound to a polymer tether is spatially
confined rather than simply reduced. We calculate the selectivity of the NPC and explore its dependence on the
size of the confinement domains. We then use probabilistic methods to determine the splitting probability and
mean first passage time (MFPT) for an individual particle to pass through the pore. Our analysis establishes
that spatial confinement can significantly reduce selectivity in a binding-diffusion model, suggesting that other
biophysical mechanisms such as interchain transfer are required.