ABSTRACT
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
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.
Subject(s)
Docosahexaenoic Acids/chemistry , Liposomes/chemistry , 1,2-Dipalmitoylphosphatidylcholine/chemistry , Lipid Bilayers/chemistry , Membrane Fluidity , Molecular Dynamics Simulation , Transition Temperature , Water/chemistryABSTRACT
Xanthones and derivatives are natural active compounds whose interest has been increased due to its several pharmacological effects. In this work, effects of hydroxy-xanthones on the physicochemical properties of dipalmitoylphosphatidylcholine (DPPC) liposomes have been investigated in terms of lipid bilayer fluidity, by means of molecular dynamics simulations and temperature dependence of zeta potential studies. Experimental results predict, in good agreement with simulations, that xanthones are able to be incorporated into DPPC liposomes with certain localization, fluidizing the bilayer. Both effects, localization and fluidity were found to be dependent of the number of hydroxilic substituents of the xanthone and the lipid phase state.
Subject(s)
1,2-Dipalmitoylphosphatidylcholine/chemistry , Lipid Bilayers/chemistry , Molecular Dynamics Simulation , Xanthones/chemistry , Xanthones/pharmacology , Chemical Phenomena/drug effects , TemperatureABSTRACT
Temperature dependence of the zeta potential (ZP) is proposed as a tool to analyze the thermotropic behavior of unilamellar liposomes prepared from binary mixtures of phosphatidylcholines in the absence or presence of ions in aqueous suspensions. Since the lipid phase transition influences the surface potential of the liposome reflecting a sharp change in the ZP during the transition, it is proposed as a screening method for transition temperatures in complex systems, given its high sensitivity and small amount of sample required, that is, 70% less than that required in the use of conventional calorimeters. The sensitivity is also reflected in the pre-transition detection in the presence of ions. Plots of phase boundaries for these mixed-lipid vesicles were constructed by plotting the delimiting temperatures of both main phase transition and pre-transition vs. the lipid composition of the vesicle. Differential scanning calorimetry (DSC) studies, although subject to uncertainties in interpretation due to broad bands in lipid mixtures, allowed the validation of the temperature dependence of the ZP method for determining the phase transition and pre-transition temperatures. The system chosen was dipalmitoylphosphatidylcholine/dimyristoyl phosphatidylcholine (DMPC/DPPC), the most common combination in biological membranes. This work may be considered as a starting point for further research into more complex lipid mixtures with functional biological importance.
Subject(s)
1,2-Dipalmitoylphosphatidylcholine/chemistry , Dimyristoylphosphatidylcholine/chemistry , Phase Transition , Unilamellar Liposomes/chemistry , Water/chemistry , Calorimetry, Differential Scanning , Electrochemical Techniques , Solutions , Static Electricity , TemperatureABSTRACT
The purpose of the work is to compare the influence of the multilamellarity, phase state, lipid head groups and ionic media on the origin of the surface potential of lipid membranes. With this aim, we present a new analysis of the zeta potential of multilamellar and unilamellar vesicles composed by phosphatidylcholines (PC) and phosphatidylethanolamines (PE) dispersed in water and ionic solutions of polarizable anions, at temperatures below and above the phase transition. In general, the adsorption of anions seems to explain the origin of the zeta potential in vesicles only above the transition temperature (Tc). In this case, the sign of the surface potential is ascribed to a partial orientation of head group moiety toward the aqueous phase. This is noticeable in PC head groups but not in PEs, due to the strong lateral interaction between PO and NH group in PE.
