TY - JOUR

T1 - Interaction of ethanol with biological membranes

T2 - the formation of non-bilayer structures within the membrane interior and their significance

AU - Gurtovenko, Andrey A.

AU - Anwar, Jamshed

PY - 2009/2/19

Y1 - 2009/2/19

N2 - To gain a better understanding of how ethanol affects biological membranes, we have performed a series of atomic-scale molecular dynamics simulations of phospholipid membranes in aqueous solution with ethanol, whose concentration was varied from 2.5 to 30 mol % (lipid-free basis). At concentrations below the threshold value of similar to 12 mol % (30.5 v/v %) ethanol induces expansion of the membrane, accompanied by a drop in the membrane thickness as well as disordering and enhanced interdigitation of lipid acyl chains. These changes become more pronounced with increase in ethanol concentration, but the bilayer structure of the membrane is maintained. Above the threshold concentration the appearance of multiple transient defects in the lipid water interface eventually gives rise to desorption and assembly of some of the lipids into non-bilayer structures within the membrane interior. These structures, being small and irregular, resemble inverted micelles and have a long-lived character. Furthermore, formation of the non-bilayer structures is accompanied by mixing of lipids that belong to the opposite membrane leaflets, thereby leading to irreversible changes in the membrane structure. Remarkably, this observation of the formation of non-bilayer structures within the membrane interior, being in good agreement with experimental data, is found to be robust with respect to both the simulation conditions (the system size and the presence of salt) and the type of lipids (phosphatidylcholine and phosphatidylethanolamine). We discuss the significance of these non-bilayer structures in relation with the well-known ability of ethanol to promote membrane hemifusion as well as with the possible role of the micelle-like structures as a delivery system for polar solutes and ions. The ethanol-induced "damage" to the bilayer structure also suggests that strong alcoholic beverages (similar to 40 v/v %) might be potentially hazardous to the epithelial tissues of the human body (such as lips, mouth, throat, gullet, and stomach) that come in direct contact with high-concentrations of ethanol.

AB - To gain a better understanding of how ethanol affects biological membranes, we have performed a series of atomic-scale molecular dynamics simulations of phospholipid membranes in aqueous solution with ethanol, whose concentration was varied from 2.5 to 30 mol % (lipid-free basis). At concentrations below the threshold value of similar to 12 mol % (30.5 v/v %) ethanol induces expansion of the membrane, accompanied by a drop in the membrane thickness as well as disordering and enhanced interdigitation of lipid acyl chains. These changes become more pronounced with increase in ethanol concentration, but the bilayer structure of the membrane is maintained. Above the threshold concentration the appearance of multiple transient defects in the lipid water interface eventually gives rise to desorption and assembly of some of the lipids into non-bilayer structures within the membrane interior. These structures, being small and irregular, resemble inverted micelles and have a long-lived character. Furthermore, formation of the non-bilayer structures is accompanied by mixing of lipids that belong to the opposite membrane leaflets, thereby leading to irreversible changes in the membrane structure. Remarkably, this observation of the formation of non-bilayer structures within the membrane interior, being in good agreement with experimental data, is found to be robust with respect to both the simulation conditions (the system size and the presence of salt) and the type of lipids (phosphatidylcholine and phosphatidylethanolamine). We discuss the significance of these non-bilayer structures in relation with the well-known ability of ethanol to promote membrane hemifusion as well as with the possible role of the micelle-like structures as a delivery system for polar solutes and ions. The ethanol-induced "damage" to the bilayer structure also suggests that strong alcoholic beverages (similar to 40 v/v %) might be potentially hazardous to the epithelial tissues of the human body (such as lips, mouth, throat, gullet, and stomach) that come in direct contact with high-concentrations of ethanol.

KW - PHOSPHOLIPID-BILAYERS

KW - PARTICLE MESH EWALD

KW - PHASE-BEHAVIOR

KW - LIPID-BILAYER

KW - MOLECULAR-DYNAMICS SIMULATIONS

KW - HYDRATION

KW - SHORT-CHAIN ALCOHOLS

KW - PHOSPHATIDYLETHANOLAMINE

KW - INTERFACIAL-TENSION

KW - PHOSPHATIDYLCHOLINE

U2 - 10.1021/jp808041z

DO - 10.1021/jp808041z

M3 - Journal article

VL - 113

SP - 1983

EP - 1992

JO - Journal of Physical Chemistry B

JF - Journal of Physical Chemistry B

SN - 1520-6106

IS - 7

ER -