Permeation through nanochannels: revealing fast kinetics.

The permeation of water soluble molecules across cell membranes is controlled by channel-forming proteins and, in particular, the channel surface determines the selectivity. An adequate method to study the properties of these channels is electrophysiology and, in particular, analyzing the ion current fluctuation in the presence of permeating solutes. Ion current fluctuation analysis provides information on possible interactions of solutes with the channel surface. Due to the limited time resolution, fast permeation events are not visible using standard techniques. Here, we demonstrate that miniaturization of the lipid bilayer; varying the temperature or changing the solvent may enhance the resolution. Although electrophysiology is considered as a single molecule technique, it does not provide atomic resolution. Molecular details of solute permeation can be revealed by combining electrophysiology and all-atom computer modeling; these methods include ion conductance, selectivity, ion pair formation, and rate limiting interactions of the solute with the channel walls during permeation.