The effect of aliphatic alcohols on fluid bilayers in unilamellar DOPC vesicles — A small-angle neutron scattering and molecular dynamics study

• Published in: Biochimica et biophysica acta 2011-09, Vol.1808 (9), p.2136-2146
• Main Authors: Klacsová, M., Bulacu, M., Kučerka, N., Uhríková, D., Teixeira, J., Marrink, S.J., Balgavý, P.
• Format: Article
• Language: English
• Subjects: Alcohol; Alcohols - chemistry; Alkanes - chemistry; Anesthetic; Carbon - chemistry; Cholesterol - chemistry; Coarse-grained simulation; Computer Simulation; Deuterium Oxide - chemistry; Dioleoylphosphatidylcholine; Lipid bilayer; Lipid Bilayers; Molecular Dynamics Simulation; Neutrons; Phosphatidylcholines - chemistry; Phosphatidylserines - chemistry; Scattering, Radiation; Scattering, Small Angle; Small-angle neutron scattering; Temperature; Water - chemistry
• ISSN: 0005-2736; 0006-3002; 1879-2642
• DOI: 10.1016/j.bbamem.2011.04.010

Small-angle neutron scattering and coarse-grained molecular dynamics simulations have been used to determine the structural parameters (bilayer thickness D, polar region thickness DH, interfacial lateral area of the unit cell AUC and alcohol partial interfacial area ACnOH) of fluid dioleoylphosphatidylcholine:dioleoylphosphatidylserine (PCPS, DOPC:DOPS=24.7mol:mol) bilayers in extruded unilamellar vesicles with incorporated aliphatic alcohols (CnOH, n=8–18 is the even number of carbons in alkyl chain). External 2H2O/H2O contrast variation experiments revealed that DH decreases as a function of alkyl chain length and CnOH:PCPS molar ratio. Using measurements at single 100% 2H2O contrast we found that (i) D decreases with CnOH:PCPS molar ratio and increases with CnOH chain length (at 0.4 molar ratio); (ii) AUC significantly increases already in the presence of shortest CnOH studied (at 0.4 molar ratio), further increase is observed with longer CnOHs and at higher molar ratios; (iii) ACnOH of alcohol molecules in PCPS bilayer increases linearly with the alkyl chain length, ACnOH obtained for CnOHs with n≤10 corresponds to ACnOH≤20Å2 — a value specific for the crystalline or solid rotator phase of alkanes. All these structural modifications induced by studied CnOHs were reproduced in MD simulations. The computational results give an accurate description of the alcohol effects at the molecular level, explaining the experimental data. The anomaly in ACnOH is discussed via the “umbrella” effect described for cholesterol. ► Neutron scattering and molecular dynamics study on structural parameters of DOPC+DOPS+CnOH (n=8–18) bilayers. ► Bilayer thickness decreases with CnOH:PCPS molar ratio and increases with CnOH chain length. ► Lateral area of the unit cell significantly increases already in the presence of C8OH. ► Alcohol partial interfacial area in bilayers increases linearly with the alkyl chain length. ► Alcohol partial interfacial area obtained for CnOHs with n≤10 corresponds to ACnOH≤20Å2.