A Fluorinated Detergent for Membrane-Protein Applications

Surfactants carrying fluorocarbon chains hold great promise as gentle alternatives to conventional hydrocarbon‐based detergents for the solubilization and handling of integral membrane proteins. However, their inertness towards lipid bilayer membranes has limited the usefulness of fluorinated surfactants in situations where detergent‐like activity is required. We demonstrate that fluorination does not necessarily preclude detergency, as exemplified by a fluorinated octyl maltoside derivative termed F6OM. This nonionic compound readily interacts with and completely solubilizes phospholipid vesicles in a manner reminiscent of conventional detergents without, however, compromising membrane order at subsolubilizing concentrations. Owing to this mild and unusual mode of detergency, F6OM outperforms a lipophobic fluorinated surfactant in chaperoning the functional refolding of an integral membrane enzyme by promoting bilayer insertion in the absence of micelles. Mild thing: Mild detergency is required for a surfactant to chaperone the functional refolding of membrane proteins into liposomes. In contrast with other surfactants carrying a lipophobic fluorinated chain, a fluorinated octyl maltoside derivative meets this condition and solubilizes phospholipid vesicles in a detergent‐like but gentle fashion.