ABSTRACT
Cholesterol is known to significantly modify both the structural and the dynamical properties of lipid membranes. On one side, the presence of free cholesterol molecules has been determined to stiffen the membrane bilayer by stretching the hydrophobic tails. Additionally, recent experimental and computational findings have made evident the fact that cholesterol also alters the dynamics and the hydration properties of the polar head groups of DPPC model lipid membranes. In turn, we have recently shown that the Omega-3 fatty acid docosahexaenoic acid, DHA, counteracts the effect of cholesterol on DPPC membrane's mechanical properties by fluidizing the bilayer. However, such behavior represents in fact a global outcome dominated by the larger lipid hydrophobic tails that neither discriminates between the different parts of the membrane nor elucidates the effect on membrane hydration and binding properties. Thus, we now perform molecular dynamics simulations to scrutinize the influence of DHA on the interfacial behavior of cholesterol-containing lipid membranes by characterizing their hydration properties and their binding to amphiphiles. We find that while cholesterol destabilizes interactions with amphiphiles and slightly weakens the lipid's hydration layer, the incorporation of DHA practically restores the interfacial behavior of pure DPPC.
Subject(s)
Docosahexaenoic Acids , Lipid Bilayers , Lipid Bilayers/chemistry , Cholesterol/chemistry , Molecular Dynamics Simulation , Software , 1,2-Dipalmitoylphosphatidylcholine/chemistryABSTRACT
This work investigates how docosahexaenoic acid (DHA) modifies the effect of Cholesterol (Chol) on the structural and dynamical properties of dipalmitoylphosphatidylcholine (DPPC) membrane. We employ low-cost and non-invasive methods: zeta potential (ZP), conductivity, density, and ultrasound velocity, complemented by molecular dynamics simulations. Our studies reveal that 30% of DHA added to the DPPC-Chol system tends to revert Chol action on a model lipid bilayer. Results obtained in this work shed light on the effect of polyunsaturated fatty acids - particularly DHA - on lipid membranes, with potential preventive applications in many diseases, e.g. neuronal as, Alzheimer's disease, and viral, as Covid-19.
Subject(s)
Cholesterol/metabolism , Docosahexaenoic Acids/metabolism , Lipid Bilayers/metabolism , Phosphatidylcholines/metabolism , Liposomes , Molecular Structure , Temperature , Ultrasonic WavesABSTRACT
Fluorescence spectroscopy and Molecular Dynamics results show that cholesterol reduces water along the chains in ether lipids by changing the water distribution pattern between tightly and loosely bound water molecules. Water distribution was followed by emission spectra and generalized polarization of 6-dodecanoyl-2-dimethyl aminonaphthalene (Laurdan) inserted in 1,2-dimiristoyl-sn-glycero-3-phosphocholine (DMPC) and 1,2-di-O-tetradecyl-sn-glycero-3-phosphocholine (14: 0 Diether PC) membranes. Molecular Dynamics simulations indicate that the action of cholesterol could be different in ether PC in comparison to ester PC. In addition, Cholesterol seems to act "per se" as an additional hydration center in ether lipids. Regardless of the phase state, cholesterol both in DMPC and 14:0 Diether PC vesicles, changed the distribution of water molecules decreasing the dipole relaxation of the lipid interphase generating an increase in the non-relaxable population. Above 10% Cholesterol/14:0 Diether PC ratio vesicles' interphase present an environment around Laurdan molecules similar to that corresponding to ester PC.
Subject(s)
Cholesterol/chemistry , Lipid Bilayers/chemistry , Phosphatidylcholines/chemistry , Spectrometry, Fluorescence , Structure-Activity RelationshipABSTRACT
This work reports the effect of hydroxy-xanthones (XAs) on 1,2-Dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and 1,2-Dimyristoyl-sn-glycero-3-phosphocholine (DMPC) bilayers as determined by ultrasound velocimetry, densimetry and molecular dynamics simulations. XAs with different number of hydroxyl group were studied. Experimental results, in good agreement with molecular dynamics simulations, revealed that the presence of XAs in the systems studied increases fluidity while simultaneously decreses the compressibility of both membranes. This ´apparent contradiction´ ceases to exist when the particular geometrical structure of the xanthones is taken into account: the planar shape of their fused aromatic rings might allow them to pack efficiently among the hydrocarbon tails of the lipids, thus decreasing compressibility, while their presence weakens or disrupts methylene-methylene interchain interactions, thus increasing membrane fluidity and decreasing their melting temperature.
Subject(s)
Lipid Bilayers/chemistry , Phosphatidylcholines/chemistry , Xanthones/chemistry , Liposomes/chemical synthesis , Liposomes/chemistry , Membrane Fluidity , Molecular Dynamics Simulation , Molecular StructureABSTRACT
Docosahexaenoic acid (DHA, 22:6) is a natural active compound that has raised considerable interest due to its several biological effects. In this work, effects of free DHA on the physicochemical properties of dipalmitoylphosphatidylcholine (DPPC) liposomes are investigated in terms of lipid membrane structure, by means of temperature-dependent zeta potential measurements, density studies and molecular dynamics simulations. Experimental results predict, in good agreement with simulations that DHA readily incorporates into DPPC liposomes, localizing at the lipid headgroup region. These data show that DHA induces changes in the lipid bilayer structure as well as in membrane fluidity.
