Partitioning of ethanol into lipid membranes and its effect on fluidity and permeability as seen by X-ray and neutron scattering

Abstract

We present a combined neutron and X-ray scattering investigation to study the effect of ethanol on the molecular structure and dynamics of lipid membranes. 1,2-Dimyristoyl-sn-glycero-3phoshatidylcholine (DMPC) powder hydrated with a 5 wt% ethanol solution (corresponding to 2 mol% of ethanol) was used in this study. From high-resolution X-ray experiments the position and partitioning of the ethanol molecules in the phospholipid bilayers was determined in their gel and fluid phases. We find that the ethanol molecules reside in the head group region of the bilayers, with 1.6 ethanol molecules per lipid molecule in the gel phase and 1.2 ethanol molecules per lipid molecule in the fluid phase. We find evidence for enhanced permeability in both fluid and gel phases of the phospholipid bilayers in the presence of ethanol molecules. Elastic and quasi-elastic neutron scattering data, obtained using a neutron backscattering spectrometer, was used to study slow, nanosecond molecular dynamics on length scales corresponding to lipid diffusion, acyl chain dynamics and solvent dynamics. While the presence of ethanol molecules had no observable effect on these types of dynamics in the fluid (L a ) phase, the membranes appeared to have a higher degree of order in gel (L b ) and ripple (P b 0 ) phases. In particular, lipid diffusion was found to be slower by a factor of two in the more rigid gel phase when ethanol was present.

Diffusion in membranes: Toward a two-dimensional diffusion map

“…1B. LET covers three orders of magnitude in time: from ∼0.5 picoseconds to almost 1 nanosecond; this timescale compliments our previous backscattering results [6]. The data and current, yet partial, analysis from this experiment on the cold neutron multi-chopper spectrometer LET at ISIS were presented at the QENS 2014/WINS 2014 conference in Autrans, France.…”

“…In previous studies, membranes were immersed in a water-ethanol solution to ensure a specific concentration of ethanol molecules in the bilayers [6,9,10]. High absorption and background in the neutron spectra is detected as a result of the large proportion of solvent.…”

“…We recently presented experimental evidence from Xray diffraction and quasi-elastic neutron scattering that ethanol enhances the permeability of membranes [6]. We determined the location and partitioning of ethanol molecules in single-component lipid bilayers.…”

Substituents modulate biphenyl penetration into lipid membranes

“…No attempt was made to remove the 3.9% ethanol from the dispersion since the ethanol facilitated the stability of the added biphenyl in solution for the subsequent fluorescence measurements. It has been shown that 4% ethanol does not significantly influence dimyristoyl PC (DMPC) conformation in vesicle dispersions [57] and shows no significant interaction with DOPC monolayers supported on Hg (data not shown).…”

Effects of Ethanol and Cholesterol on Thermotropic Phase Behavior of Ion-Pair Amphiphile Bilayers

“…On the other hand, ethanol binding to the lipid-water interface of phospholipid bilayers may significantly altered the orientation of the bilayer headgroups and disordered the entire lengths of the hydrocarbon chains 37 . Pronounced increase in the area per lipid 37,38 , decrease in the ordering of the chains 37,39 , and higher fluidity and permeability of the bilayers 38,39 were attributed to ethanol and other short-chain alcohols. The monotonous lowering of T m exhibited by IPA bilayers, therefore, is possibly due to the same disordering effects of ethanol on lipid bilayers.…”