Detergent Effects on Membranes at Sub-Solubilizing Concentrations: Transmembrane Lipid Motion, Bilayer Permeabilization and Vesicle Lysis/reassembly are Independent Phenomena

Abstract

Soluble amphiphiles, or detergents, are known to produce a number of structural and dynamic effects on membranes, even at concentrations below those causing membrane solubilization, i.e. at the so-called stage I of detergent-membrane interaction. The main sub-solubilizing detergent effects on membranes are: transmembrane lipid motion (flip-flop), breakdown of the membrane permeability barrier leakage, and vesicle lysis / reassembly. For a proper understanding of membrane solubilization by detergents it is important to assess whether the various effects seen at sub-solubilizing surfactant concentrations occur independently from each other, or else they are interconnected by cause-effect relationships, so that they can be interpreted as necessary steps in the overall process of solubilization. In order to answer this question we have explored the three above-mentioned effects, i.e. flip-flop, leakage and lysis / reassembly, apart from solubilization, in model (large unilamellar vesicles) and cell (erythrocyte) membranes. Five structurally different surfactants, namely chlorpromazine, imipramine, Triton X-100, sodium dodecylsulfate and sodium deoxycholate have been used. Each of them behaves in a unique way. Our results reveal that lipid flip-flop, vesicle leakage and vesicle lysis/reassembly are independent phenomena between them and with respect to bilayer solubilization, so that they can not be considered as necessary stages of a higher-order unified process of membrane solubilization by detergents.