Nuclear Pore Complex (NPC) is a biological “nano-machine” that controls the macromolecular transport between the cell nucleus and the cytoplasm. 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 aspect of transport is the interaction of the transported molecules with the meshwork of unfolded, natively unstructured proteins that cover the lumen of the Nuclear Pore Complex. Recently, the Nuclear Pore Complex inspired creation of artificial selective nano-channels that mimic its structure and function for nano-technology applications.
Despite recent advances, mechanistic understanding of transport through the Nuclear Pore Complex, and in particular its selectivity, is still lacking. I will present a theoretical framework that explains the mechanism of selectivity of transport through the Nuclear Pore Complex and related artificial nano-channels. The theory provides a general physical mechanism for selectivity based on the differences in the interaction strength of the transported molecules with the unfolded proteins within the NPC. In particular, the theory explains how such channels can remain selective in the presence of vast amounts of non-specific noise. The theoretical predictions have been verified in experiments with bio-mimetic molecular nano-channels. Finally, I will discuss how the general theory can be tied to the underlying conformational dynamics of the unfolded proteins within the NPC.