Real-time monitoring the staged interactions between cationic surfactants and a phospholipid bilayer membrane

The cationic surfactant-lipid interaction directs the development of novel types of nanodrugs or nanocarriers. The membrane action of cationic surfactants also has a wide range of applications. In this work, combining a photo-voltage transient method with the traditional dynamic giant unilamellar vesicle (GUV) leakage assay and molecular dynamics (MD) simulations, we monitored the molecular actions of a representative cationic surfactant, tetradecyl trimethyl ammonium bromide (TTAB), in a wide concentration range (i.e., 0.5 μM-10 mM), on a phospholipid bilayer membrane in real time. With low concentrations (e.g., ≤10 μM), TTAB performed a three-stage acting process, including the structural-disturbance-dominated, adsorption-dominated, and dynamic equilibrium stages. At higher concentrations (e.g., ≥100 μM), this process was accelerated to two stages. Furthermore, TTAB induced deformation and even rupture of the membrane, due to the asymmetric disturbance of surfactant molecules on the two leaflets of a bilayer. All these disturbances induced membrane permeabilization, and the times at which these transitions occurred are given. This work provides information on time and molecular mechanism during the membrane actions of cationic surfactants, and provides a simple and real-time method in studying the dynamic processes at the membrane interface.