Dynamics and free energy of polymers partitioning into a nanoscale pore

Membrane-bound proteinaceous nanoscale pores allow us to simultaneously observe the thermodynamic and kinetic properties of differently sized polymers within their confines. We determine the dynamic partitioning of poly(ethylene glycol) (PEG) into the pore formed by Staphylococcus aureus alpha-toxin and evaluate the free energy of polymer confinement by measuring polymer-induced changes to the pore's ionic conductance. The free energy deduced from the partition coefficient has a sharper dependence on polymer length (or weight) than scaling theory predicts. Moreover, the polymer-induced conductance fluctuations show a striking nonmonotonic dependence on the polymer molecular weight. The movement of polymer inside the pore is characterized by a diffusion coefficient that is orders of magnitude smaller than that for polymer in the bulk aqueous solution, which suggests that PEG has an attractive interaction with the pore. Using an ad-hoc approach,we show that a simple molecular weight-dependent modification of the polymer's diffusion coefficient accounts for these results, but only qualitatively. Given that PEG associates with hydrophobic regions in proteins, we also conclude that, contrary to the conventional view of ion channels, the aqueous cavity of the alpha-toxin pore's interior is, to some extent, hydrophobic.