title: Model inspired by nuclear pore complex suggests possible roles for nuclear transport receptors in determining its structure.
abstract: Nuclear transport receptors (NTRs) mediate nucleocytoplasmic transport via their affinity for unstructured proteins (polymers) in the nuclear pore complex (NPC). Here, we have modeled the effect of NTRs on polymeric structure in the nanopore confinement of the NPC central conduit. The model explicitly takes into account inter- and intramolecular interactions, as well as the finite size of the NTRs (∼20% of the NPC channel diameter). It reproduces various proposed scenarios for the channel structure, ranging from a central polymer condensate (selective phase) to brushlike polymer arrangements localized at the channel wall (virtual gate, reduction of dimensionality), with the transport receptors lining the polymer surface. In addition, it predicts a new structure in which NTRs become an integral part of the transport barrier by forming a cross-linked network with the unstructured proteins stretching across the pore. The model provides specific and distinctive predictions for the equilibrium spatial distributions of NTRs for these different scenarios that can be experimentally verified by, e.g., superresolution fluorescence microscopy. Moreover, it suggests mechanisms by which globular macromolecules (colloidal particles) can cause polymer-coated nanopores to switch between open and closed configurations, a possible explanation of the biological function of the NPC, and suggests potential technological applications for filtration and single-molecule sensing.
authors.affiliation: London Centre for Nanotechnology and Department of Physics and Astronomy, University College London, London, United Kingdom. Electronic address: d.osmanovic@ucl.ac.uk.
authors.forename: Dino
authors.initials: D
authors.lastname: Osmanović
authors.affiliation: London Centre for Nanotechnology and Department of Physics and Astronomy, University College London, London, United Kingdom.
authors.forename: Ian J
authors.initials: IJ
authors.lastname: Ford
authors.affiliation: London Centre for Nanotechnology and Department of Physics and Astronomy, University College London, London, United Kingdom.
authors.forename: Bart W
authors.initials: BW
authors.lastname: Hoogenboom
mesh_terms: D021581:Active Transport, Cell Nucleus; D000818:Animals; D008954:Models, Biological; D022022:Nuclear Pore / Q000737:chemistry* / Q000378:metabolism