Thermodynamics of lipid multi-lamellar vesicles in presence of sterols at high hydrostatic pressure

Abstract

We compared the effect of cholesterol at different concentration on the phase behaviour of DMPC (1,2-dimyristoyl-sn-glycero-3-phosphocholine) multilamellar vesicles. We used pressure perturbation differential scanning calorimetry (PPC) that studies a system on the whole by giving access to relevant thermodynamic quantities, and elastic incoherent neutron scattering (EINS) that probes local motions of a system at the atomic level by allowing extraction of dynamical parameters. PPC revealed that the volume expansion coefficient of DMPC and DMPC/Cholesterol samples with 13 and 25 mol% cholesterol is a linear function of the heat capacity measured by differential scanning calorimetry. Neutron backscattering spectroscopy showed that the mean square displacements of H atoms do exhibit an increase with temperature and a decrease under increasing pressure. Cholesterol added at concentrations of 25 and 50 mol% led to suppression of the main phase transition. Taking advantage of these results, the present study aims (i) to show that calorimetry and EINS using the Bicout and Zaccai model equally permit to get access to thermodynamic quantities characterizing pure DMPC and DMPC/cholesterol mixtures, thus directly confirming the theoretical method, and (ii) to validate our approach as function of temperature and of pressure, as both are equally important and complementary thermodynamic variables.

Protein Backbone and Average Particle Dynamics in Reconstituted Discoidal and Spherical HDL Probed by Hydrogen Deuterium Exchange and Elastic Incoherent Neutron Scattering

“…Note that lipid phase transitions are observed in the dynamics of pure lipid samples [66], but are hardly visible in mixed systems, as in the present case [4]. Thus, during the gradual change in temperature, we did not register typical phase transitions for POPC or cholesteryl ester core that occurred at~270 K and~306 K, respectively.…”

“…HDLs have the highest protein-to-lipid ratio and are the smallest and densest of all lipoprotein classes. Pure lipids are highly dynamic at ambient temperatures [4,66,70,71], and one would expect that the mobility of lipoproteins to increase with the increase in their lipid content. For example, rHDL has~26% protein mass and~74% lipid mass, whereas rsHDL has~37% protein mass and~63% lipid mass, so rHDL should be softer and more flexible than rsHDL.…”

“…For example, highly dynamic lipoproteins make excellent lipid transporters in the circulatory system. Lipid-containing biomolecules constitute attractive targets for investigation by EINS because their softness and flexibility impact their biological functions, as shown in earlier studies on 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) vesicles [4], very-low-density lipoproteins (VLDL), and low-density lipoproteins (LDL) [5][6][7].…”

High-resolution neutron spectroscopy using backscattering and neutron spin-echo spectrometers in soft and hard condensed matter

“…Increasing in complexity, lipid membranes can undergo various, and sometimes sizeable and physiologically important, changes when small molecules or peptides are present. Examples include antimicrobial peptides 67 , neurotoxic amyloid-β,36 melittin 68 , the anaesthetic ethanol 69 or even cholesterol under pressure 70 . Furthermore, new insight into the role of rafts was obtained through NSE measurements of the lateral diffusion coefficients in a phase-separated lipid mixture.…”

Microfluidic technologies for the synthesis and manipulation of biomimetic membranous nano-assemblies

“…88 Large values for spontaneous curvature (H 0 ) and bending moduli, in addition to weak inter-bilayer repulsive forces, are thought to provide a thermodynamic explanation for preferential MLV formation at equilibrium, and as such their formation is highly dependent on the molecular properties of chosen amphiphiles. 90,91 To the best of our knowledge, no examples exist for the controlled preparation of either nano-scale or micron-scale MLVs using bulk methods. This is presumably due to the absence of control one has over the exact number of bilayers present in generated vesicles, understandably eliminating the possibility of designing functional MLV particles and pursuing this architecture further.…”