Red-light-catalyzed photolipid switching enables leaflet-selective control of membrane mechanics

Abstract

Azobenzene photolipids are versatile actuators of membrane mechanics and protein function, yet long-wavelength control and leaflet-selective perturbations remain difficult to impose. Here, we address both limitations. First, we confirm that red-light excitation of a lipidated Nile Blue derivative (NB-lipid) catalyzes rapid cis[->]trans photoisomerization of co-localized azobenzene photolipids in planar bilayers without requiring covalent conjugation. Second, we demonstrate that photocatalysis is predominantly intraleaflet, enabling leaflet-selective actuation by incorporating the membrane-targeted chromophore into only one bilayer leaflet. This enables on-demand and rapid writing of transbilayer mechanical asymmetry, which we track via lock-in capacitance signatures. Critically, symmetric and asymmetric leaflet mechanical perturbations can be evoked within the same membrane by illuminating with blue or red light, respectively. For electron-rich azobenzenes, the anticipated singlet-state photoredox pathway is expected to limit triplet-associated photodamage. Repeated, reversible modulation of gramicidin A, a mechanosensitive peptide ion channel susceptible to reactive oxygen species, supports the compatibility of photocatalysis with membrane protein function. Our results establish a novel tool for dissecting the role of dynamic leaflet-specific mechanical changes in membrane remodeling and protein function.

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