A saturated FG-repeat hydrogel can reproduce the permeability properties of nuclear pore complexes.

The permeability barrier of nuclear pore complexes (NPCs) controls the exchange between nucleus and cytoplasm. It suppresses the flux of inert macromolecules > or = 30 kDa but allows rapid passage of even very large cargoes, provided these are bound to appropriate nuclear transport receptors. We show here that a saturated hydrogel formed by a single nucleoporin FG-repeat domain is sufficient to reproduce the permeability properties of NPCs. Importin beta and related nuclear transport receptors entered such hydrogel >1000x faster than a similarly sized inert macromolecule. The FG-hydrogel even reproduced import signal-dependent and importin-mediated cargo influx, allowing importin beta to accelerate the gel entry of a large cognate cargo more than 20,000-fold. Intragel diffusion of the importin beta-cargo complex occurred rapidly enough to traverse an NPC within approximately 12 ms. We extend the "selective phase model" to explain these effects.