TY - JOUR

T1 - Interaction of oleic acid with dipalmitoylphosphatidylcholine (DPPC) bilayers simulated by molecular dynamics

AU - Notman, Rebecca

AU - Noro, Massimo G.

AU - Anwar, Jamshed

PY - 2007/11/8

Y1 - 2007/11/8

N2 - The fatty acid oleic acid (OA) is known to modulate the structure of membranes, which forms the basis for a number of its important applications including its use as a therapeutic supplement to reduce the risk of cardiovascular disease, in molecule delivery systems such as liposomes, and as a skin permeability enhancer. While a number of studies have investigated the effect of OA on lipid membranes, our understanding of its mechanisms of action at the molecular level remains rudimentary. We have carried out molecular dynamics simulations using coarse-grained models to investigate the interactions of OA at a range of concentrations with a dipalmitoylphosphatidylcholine (DPPC) bilayer in the liquid-crystalline phase. We have also investigated the relative permeability of the bilayers to model hydrophilic and hydrophobic penetrants by means of chemical potential calculations. The results indicate that OA is able to disperse homogeneously into the bilayer at all concentrations without much perturbation. OA appears to slightly weaken the lateral forces between lipid headgroups, and as the concentration of OA increases this manifests itself as a slight decrease in the area compressibility modulus and a minor increase in the diffusion rate of the OA molecules. While the chemical potential profiles showed little or no variation as a function of OA concentration, the frequency of water permeation events was found to double, indicating some OA-induced permeability enhancement. The study suggests that physiological effects of OA are probably more subtle rather than via gross perturbation of the structure, or that its significant effects are restricted to more condensed membrane structures such as the gel phase.

AB - The fatty acid oleic acid (OA) is known to modulate the structure of membranes, which forms the basis for a number of its important applications including its use as a therapeutic supplement to reduce the risk of cardiovascular disease, in molecule delivery systems such as liposomes, and as a skin permeability enhancer. While a number of studies have investigated the effect of OA on lipid membranes, our understanding of its mechanisms of action at the molecular level remains rudimentary. We have carried out molecular dynamics simulations using coarse-grained models to investigate the interactions of OA at a range of concentrations with a dipalmitoylphosphatidylcholine (DPPC) bilayer in the liquid-crystalline phase. We have also investigated the relative permeability of the bilayers to model hydrophilic and hydrophobic penetrants by means of chemical potential calculations. The results indicate that OA is able to disperse homogeneously into the bilayer at all concentrations without much perturbation. OA appears to slightly weaken the lateral forces between lipid headgroups, and as the concentration of OA increases this manifests itself as a slight decrease in the area compressibility modulus and a minor increase in the diffusion rate of the OA molecules. While the chemical potential profiles showed little or no variation as a function of OA concentration, the frequency of water permeation events was found to double, indicating some OA-induced permeability enhancement. The study suggests that physiological effects of OA are probably more subtle rather than via gross perturbation of the structure, or that its significant effects are restricted to more condensed membrane structures such as the gel phase.

KW - MEMBRANES

KW - LATERAL DIFFUSION

KW - AIR-WATER-INTERFACE

KW - HUMAN-SKIN

KW - PENETRATION ENHANCERS

KW - STRATUM-CORNEUM

KW - PHASE

KW - COARSE-GRAINED MODEL

KW - SURFACE-TENSION

KW - MIXED MONOLAYERS

U2 - 10.1021/jp0723564

DO - 10.1021/jp0723564

M3 - Journal article

VL - 111

SP - 12748

EP - 12755

JO - Journal of Physical Chemistry B

JF - Journal of Physical Chemistry B

SN - 1520-6106

IS - 44

ER -