Conjugated double bonds in lipid bilayers: A molecular dynamics simulation study

Abstract

Conjugated linoleic acids (CLA) are found naturally in dairy products. Two isomers of CLA, that differ only in the location of cis and trans double bonds, are found to have distinct and different biological effects. The cis 9 trans 11 (C9T11) isomer is attributed to have the anti-carcinogenic effects, while the trans 10 cis 12 (T10C12) isomer is believed to be responsible for the anti-obesity effects. Since dietary CLA are incorporated into membrane phospholipids, we have used Molecular Dynamics (MD) simulations to investigate the comparative effects of the two isomers on lipid bilayer structure. Specifically, simulations of phosphatidylcholine lipid bilayers in which the sn-2 chains contained one of the two isomers of CLA were performed. Force field parameters for the torsional potential of double bonds were obtained from ab initio calculations. From the MD trajectories we calculated and compared structural properties of the two lipid bilayers, including areas per molecule, density profiles, thickness of bilayers, tilt angle of tail chains, order parameters profiles, radial distribution function (RDF) and lateral pressure profiles. The main differences found between bilayers of the two CLA isomers, are (1) the order parameter profile for C9T11 has a dip in the middle of sn-2 chain while the profile for T10C12 has a deeper dip close to terminal of sn-2 chain, and (2) the lateral pressure profiles show differences between the two isomers. Our simulation results reveal localized physical structural differences between bilayers of the two CLA isomers that may contribute to different biological effects through differential interactions with membrane proteins or cholesterol.

Assessment of the encapsulation effect of phenolic compounds from Spirulina sp. LEB-18 on their antifusarium activities

“…Changes in lipid shapes related to the insertion of an exogenous molecule have already been discussed for fatty acids and smaller compounds, such as flavonoids (Zhao, Subbaiah, Chiu, Jakobsson & Scott., 2011;Saija et al, 1995;Muranushi, Takagi, Muranishi & Sezaki, 1981). Considering that the fungi membrane also comprises ergosterol, which has marginal membranecondensing effects and gives less stability to phospholipid membranes, the release of the phenolic extract into the fungi membrane may require an area expansion which can easily destabilize, disrupt and lyse it.…”

Molecular dynamic simulation study of cholesterol and conjugated double bonds in lipid bilayers

“…[11] Here we summarize simulation methodology and force fields that are described in more detail in the earlier paper. The force-field parameters used for this work were taken from the newly developed GROMOS 43A1-S3 parameter set [27].…”

“…The calculations of these parameters was done following the procedure used for the 43A1-S3 force field [27]. In our earlier paper [11] we provided a detailed description of the procedure. For bonding parameters not part of the -CH=CH-CH=CH- dihedral we used existing parameters in the 43A1-S3 force field, including parameters for the dihedrals that are next to, but do not include, double bond carbons.…”

“…In this paper, we focus on linoleic acids cis 9 trans 11 and trans 10 cis 12 as these two CLA isomers bear important and interesting physiologically functions. We extend our earlier work [11] to study the potential interactions of cholesterol with conjugated double bonds brought to polyunsaturated lipid bilayer. We study the effect of cholesterol on the structure of CLA-PC bilayers of both isomers at different cholesterol concentrations, and we examine CLA-cholesterol interactions in atomistic detail.…”

“…The mechanism of action, and the molecular basis for the divergent effects of CLA isomers remain unclear, despite these and other studies in experimental animals and cultured cells. Although it is possible that at least some of the effects of CLA are through modification of membrane structure and function [7, 8, 9, 10] our earlier MD study of pure bilayers composed of the two isomers revealed very little difference in structural and dynamical properties [11]. Since Cholesterol (Chol)comprises approximately 25–40 mol % of the lipid portion of the mammalian plasma membranes, and is thought to modulate the physico–chemical properties required for cell viability and proliferation, it is natural to next consider the interactions of the two isomers with Chol.…”