Using charge to control the functional properties of self-assembled nanopores in membranes.

Control of function in self-assembled molecular structures is a major challenge in supramolecular chemistry. [ 1–4 ] Ion channels, for instance, are pore-forming nanostructures typically comprising multiple molecular subunits assembled via noncovalent interactions. [ 5 ] These pores function by facilitating a fl ux of ions across the hydrophobic barrier of a lipid bilayer. For over a decade, many groups have attempted to mimic the functional properties of ion channels by engineering molecular assemblies that are capable of inducing transmembrane ion fl ux across lipid bilayers. [ 6–30 ] A major goal for engineered ion channels is to control such transmembrane ion fl uctuations dynamically. [ 13 , 22 , 27–29 , 31–35 ] In nature, ion channels typically alter their ion conducting functional properties in response to external stimuli with the aid of specifi c chemical groups precisely located within the assembled structure. [ 5 ] Recently, we have reported the capability to control the single channel conductance ( γ , Figure 1 B) of ion channels derived from gramicidin A (gA, a natural ion-channel-forming peptide [ 5 , 36,37 ] ) in artifi cial bilayers by manipulating the electrical charge of functional groups attached near the opening of the pore (i.e., on the C-terminus of gA). [ 16,17 , 38–42 ] Here, we demonstrate that C-terminal charged groups on gA can also affect the average channel lifetime ( τ , Figure 1 C) of conducting gA dimers. We show that this effect is fundamentally interesting and useful for sensing applications (here, for sensing specifi c wavelengths of light). Channel lifetime represents a second important parameter, in addition to conductance, which dictates the overall functional properties of these self-assembled pores. We present a method to control the lifetime of a gA channel dynamically and reversibly by introducing a light-sensitive molecular switch at the opening of the pore. This switch functions by photochemically controlling the charge presented on the C-terminus of gA.