Alcohol Effects on Trans-Nuclear Membrane Transport

The nuclear pore complex (NPC) forms the size selective gate for transport between the nucleus and cytoplasm. Transport is regulated by phenylalanine-glycine rich natively unfolded proteins which form a mesh-like barrier. While the size selective permeability mechanism is poorly understood, experimental evidences suggests that weak hydrophobic interactions between FG-Nups form a sieve to keep large molecules from entering NPC. This mechanism is supported by experimental observations that certain alcohols of increasing hydrophobicity diminish the permeability barrier. We investigate the interactions between constituent amino acids in FG-Nups and cosolvent moderated interactions using molecular simulations. We find that the extent of clustering of hydrophobic side chains is enhanced by alcohols, and that this clustering correlates with experimental observations that the permeability barrier drops. Our simulations suggest then that decreased selectivity is a result of holes opening within the FG-Nup mesh providing pathways for trans nuclear membrane transport.