Effects of dimethyl sulfoxide in cholesterol-containing lipid membranes: a comparative study of experiments in silico and with cells

• Published in: PloS one 2012-07, Vol.7 (7), p.e41733
• Main Authors: de Ménorval, Marie-Amélie, Mir, Lluis M, Fernández, M Laura, Reigada, Ramon
• Format: Article
• Language: English
• Subjects: Analysis; Animals; Bicapes lipídiques; Biology; Boundary conditions; Calcium; Calcium ions; Calcium permeability; Cell culture; Cell Line; Cell Membrane - chemistry; Cell Membrane - drug effects; Cell Membrane - metabolism; Cell Membrane Permeability - drug effects; Cell membranes; Chemistry; Cholesterol; Cholesterol - chemistry; Cholesterol - metabolism; Colesterol; Comparative studies; Computational Biology; Cricetinae; Deoxyribonucleic acid; Dimethyl sulfoxide; Dimethyl Sulfoxide - chemistry; Dimethyl Sulfoxide - metabolism; Dimethyl Sulfoxide - pharmacology; DNA; Dose-Response Relationship, Drug; Drugs; Experiments; Fatty acids; Hydration; Iodides; Lipid bilayers; Lipid Bilayers - chemistry; Lipid Bilayers - metabolism; Lipid membranes; Lipid peroxidation; Lipids; Loosening; Lípids; Membrane permeability; Membranes; Membranes cel·lulars; Molecular Conformation; Molecular dynamics; Molecular Dynamics Simulation; Permeabilitat; Permeability; Phase transitions; Physics; Pore formation; Porosity; Simulation; Solvents; Studies; Sulfoxides; Trends
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0041733

Dimethyl sulfoxide (DMSO) has been known to enhance cell membrane permeability of drugs or DNA. Molecular dynamics (MD) simulations with single-component lipid bilayers predicted the existence of three regimes of action of DMSO: membrane loosening, pore formation and bilayer collapse. We show here that these modes of action are also reproduced in the presence of cholesterol in the bilayer, and we provide a description at the atomic detail of the DMSO-mediated process of pore formation in cholesterol-containing lipid membranes. We also successfully explore the applicability of DMSO to promote plasma membrane permeability to water, calcium ions (Ca(2+)) and Yo-Pro-1 iodide (Yo-Pro-1) in living cell membranes. The experimental results on cells in culture can be easily explained according to the three expected regimes: in the presence of low doses of DMSO, the membrane of the cells exhibits undulations but no permeability increase can be detected, while at intermediate DMSO concentrations cells are permeabilized to water and calcium but not to larger molecules as Yo-Pro-1. These two behaviors can be associated to the MD-predicted consequences of the effects of the DMSO at low and intermediate DMSO concentrations. At larger DMSO concentrations, permeabilization is larger, as even Yo-Pro-1 can enter the cells as predicted by the DMSO-induced membrane-destructuring effects described in the MD simulations.