Photoswitchable Detergents for Light‐Controlled Liposome Lysis and Channel Gating

Modulation of membrane properties via photoswitchable lipids has attracted attention due to the unparalleled spatiotemporal resolution of their functional control. Beside lipids, detergents are another prominent class for selective membrane perturbations owing to their ease of handling and spontaneous insertion in lipid bilayers. Herein, we describe the synthesis and characterization of three classes of visible light-sensitive surfactants with various azobenzene tail chain lengths. The photoswitchable detergents show water-solubility and micellization as well as undergo reversible isomerization under blue-/green light illumination. We demonstrate that the light-induced structural change of azobenzene can lead to vesicle rupture, making them a tool for controlled cargo release from vehicles. Via spontaneous insertion into the plasma membrane of mammalian cells transiently transfected with MscL, we used the azobenzene-derived detergents to optically activate the transmembrane mechanosensitive channel. This led to the rapid controlled uptake of membrane-impermeable molecules. Since detergents are extensively used in biochemistry and biotechnology, we propose that the photoswitchable detergents will be useful tools for the spatiotemporal modulation of membrane properties. Additionally, our work provides a design strategy for new detergents in membrane (protein) research.