Phototriggered proton-selective carrier currents through photoswitchable membranes

Controlling the flux of specific ions across lipid bilayers is a central challenge for cellular life. Here, we present a general strategy for the precise, noninvasive, and reversible photoregulation of specific ion transport across lipid bilayer membranes: using embedded azobenzene-containing photolipids as dopants that effectively photo-control the membrane permeation of specific ion carriers. Photolipid (OptoDArG) embedding and photoisomerization causes only minor changes in background ion conductance, consistent with classical models of membrane transport wherein small changes in bilayer thickness have little effect on ion permeability. Yet, in the presence of ion carriers, photoisomerization instead results in order-of-magnitude jumps in ion flux. These jumps are observed with both cationic and anionic carriers; particular protonophores deliver exceptional performance, with proton currents amplified by up to ≈200-fold upon UV illumination yet reversed by blue light exposure. A model in which interfacial uptake and release reactions are modulated by light-induced membrane changes explains these results. Doping photolipids together with well-established selective ion carriers into membranes thus presents a flexible and general chemical strategy for reversible, millisecond-scale photoregulation of specific ion trans-port across lipid bilayers. It achieves large currents, long-lasting effects, its ion scope is easily tuned by carrier choice, no genetic modifications are needed, and it has the potential to harness recent photoswitch advances to rationally shift its single-photon action spectra from the UV/Vis right up to the NIR/SWIR: a convenient all-chemical approach toward light-based ion permeability regulation in the biological or synthetic cell.