Transport by he Nuclear Pore Complex: simple physics of a complex biomachine

Abstract: Nuclear Pore Complex (NPC) is a biological “nano-machine” that controls the  transport between the cell nucleus and the cytoplasm and is involved in a large number of regulatory processes in the cell. It is a remarkable device that combines selectivity with robustness and speed. Unlike many other biological nano-channels, it functions without direct input of metabolic energy and without transitions of the gate from a ‘closed’ to an ‘open’ state during transport. The key, and unique, aspect of transport is the interaction of the cargo-carrying transport factors with the unfolded, natively unstructured proteins that partially occlude the channel of the NPC and its nuclear and cytoplasmic exits. Recently, the Nuclear Pore Complex inspired creation of artificial selective nano-channels that mimic its structure and function for nano-technology applications.

Mechanistic understanding of the transport through the Nuclear Pore Complex, and in particular its selectivity is still lacking. Conformational transitions of the unfolded proteins of the NPC, induced by the transport factors, have been hypothesized to underlie the transport mechanism and its selectivity. These conformational changes are hard to access in vivo; they have been investigated in vitro, generating apparently contradictory results. I will present a theoretical framework that explains the mechanism of selectivity of transport through the NPC and related artificial nano-channels. The theory provides a general physical mechanism for selectivity (even in presence of noise) based on the differences in the interaction strength of the transported molecules with the polymer-like unfolded proteins within the NPC. The theoretical predictions have been verified in experiments with bio-mimetic molecular nano-channels.