Phototriggered proton-selective carrier currents through photoswitchable membranes

The regulation of ion transport across biological membranes using light is a powerful research tool with potential therapeutic applications. Microbial channelrhodopsins, widely used in optoge-netics, enable passive photocurrents that facilitate advanced studies of synaptic plasticity and neuronal connectivity. However, their applicability is limited by the need for genetic transfection to introduce channelrhodopsins into target cells. Here, we present a synthetic alternative combining small-molecule carriers with azobenzene-containing photolipids (OptoDArG) to achieve rapid and reversible ion-selective permeability modulation by light. Incorporating a novel lipidated nile blue derivative (NB-lipid) into photoswitchable bilayers enabled fully reversible ≈200-fold on–off modulation of H ⁺ currents under UV and blue light illumination. The transport kinetics classify NB-lipids as cationic protonophores, demonstrating high sensitivity to OptoDArG-mediated changes in lipid packing and bilayer thickness. Another protonophore, carbonyl cyanide m -chlorophenylhydrazone (CCCP), exhibited similar sensitivity, though to a lesser extent. This concept extends beyond protonophores: valinomycin-mediated K ⁺ currents showed several-fold increases under UV light, rapidly reversed by blue light-induced generation of OptoDArG’s trans photoisomer. Our approach demonstrates that rapid, non-invasive, spatially precise, and reversible light-triggered currents can be achieved without genetic modifications. This strategy, exemplified by H ⁺ -selective currents, may be extended to other ions through tailored carrier design.