Lateral-Pressure Profiles in Cholesterol-DPPC Bilayers

By means of atomistic molecular dynamics simulations, we study cholesterol-DPPC (dipalmitoyl phosphatidylcholine) bilayers of different composition, from pure DPPC bilayers to a 1:1 mixture of DPPC and cholesterol. The lateral-pressure profiles through the bilayers are computed and separated into contributions from the different components. We find that the pressure inside the bilayer changes qualitatively for cholesterol concentrations of about 20% or higher. The pressure profile then turns from a rather flat shape into an alternating sequence of regions with large positive and negative lateral pressure. The changes in the lateral-pressure profile are so characteristic that specific interaction between cholesterol and molecules such as membrane proteins mediated solely via the lateral-pressure profile might become possible

Dynamics of Vesicle Formation from Lipid Droplet: Mechanism and Controllability

A coarse-grained model developed by Marrink et al. [J. Phys. Chem. B 111, 7812 (2007)] is applied to investigate vesiculation of lipid [dipalmitoylphosphatidylcholine (DPPC)] droplets in water. Three kinds of morphologies of micelles are found with increasing lipid droplet size. When the initial lipid droplet is smaller, the equilibrium structure of the droplet is a spherical micelle. When the initial lipid droplet is larger, the lipid ball starts to transform into a disk micelle or vesicle. The mechanism of vesicle formation from a lipid ball is analyzed from the self-assembly of DPPC on the molecular level, and the morphological transition from disk to vesicle with increasing droplet size is demonstrated. Importantly, we discover that the transition point is not very sharp, and for a fixed-size lipid ball, the disk and vesicle appear with certain probabilities. The splitting phenomenon, i.e., the formation of a disk/vesicle structure from a lipid droplet, is explained by applying a hybrid model of the Helfrich membrane theory. The elastic module of the DPPC bilayer and the smallest size of a lipid droplet for certain formation of a vesicle are successfully predicted.Comment: 22 pages, 11 figures Submitted to J. Chem. Phy

Coupling between pore formation and phase separation in charged lipid membranes

We investigated the effect of charge on the membrane morphology of giant unilamellar vesicles (GUVs) composed of various mixtures containing charged lipids. We observed the membrane morphologies by fluorescent and confocal laser microscopy in lipid mixtures consisting of a neutral unsaturated lipid [dioleoylphosphatidylcholine (DOPC)], a neutral saturated lipid [dipalmitoylphosphatidylcholine (DPPC)], a charged unsaturated lipid [dioleoylphosphatidylglycerol (DOPG$^{\scriptsize{(-)}}$)], a charged saturated lipid [dipalmitoylphosphatidylglycerol (DPPG$^{\scriptsize{(-)}}$)], and cholesterol (Chol). In binary mixtures of neutral DOPC/DPPC and charged DOPC/DPPG$^{\scriptsize{(-)}}$, spherical vesicles were formed. On the other hand, pore formation was often observed with GUVs consisting of DOPG$^{\scriptsize{(-)}}$ and DPPC. In a DPPC/DPPG$^{\scriptsize{(-)}}$/Chol ternary mixture, pore-formed vesicles were also frequently observed. The percentage of pore-formed vesicles increased with the DPPG$^{\scriptsize{(-)}}$ concentration. Moreover, when the head group charges of charged lipids were screened by the addition of salt, pore-formed vesicles were suppressed in both the binary and ternary charged lipid mixtures. We discuss the mechanisms of pore formation in charged lipid mixtures and the relationship between phase separation and the membrane morphology. Finally, we reproduce the results seen in experimental systems by using coarse-grained molecular dynamics simulations.Comment: 34 pages, 10 figure

A supramolecular radical cation: folding-enhanced electrostatic effect for promoting radical-mediated oxidation.

We report a supramolecular strategy to promote radical-mediated Fenton oxidation by the rational design of a folded host-guest complex based on cucurbit[8]uril (CB[8]). In the supramolecular complex between CB[8] and a derivative of 1,4-diketopyrrolo[3,4-c]pyrrole (DPP), the carbonyl groups of CB[8] and the DPP moiety are brought together through the formation of a folded conformation. In this way, the electrostatic effect of the carbonyl groups of CB[8] is fully applied to highly improve the reactivity of the DPP radical cation, which is the key intermediate of Fenton oxidation. As a result, the Fenton oxidation is extraordinarily accelerated by over 100 times. It is anticipated that this strategy could be applied to other radical reactions and enrich the field of supramolecular radical chemistry in radical polymerization, photocatalysis, and organic radical battery and holds potential in supramolecular catalysis and biocatalysis

Coarse-Grained Model for Phospholipid/Cholesterol Bilayer

We construct a coarse-grained (CG) model for dipalmitoylphosphatidylcholine (DPPC)/cholesterol bilayers and apply it to large-scale simulation studies of lipid membranes. Our CG model is a two-dimensional representation of the membrane, where the individual lipid and sterol molecules are described by point-like particles. The effective intermolecular interactions used in the model are systematically derived from detailed atomic-scale molecular dynamics simulations using the Inverse Monte Carlo technique, which guarantees that the radial distribution properties of the CG model are consistent with those given by the corresponding atomistic system. We find that the coarse-grained model for the DPPC/cholesterol bilayer is substantially more efficient than atomistic models, providing a speed-up of approximately eight orders of magnitude. The results are in favor of formation of cholesterol-rich and cholesterol-poor domains at intermediate cholesterol concentrations, in agreement with the experimental phase diagram of the system. We also explore the limits of the novel coarse-grained model, and discuss the general validity and applicability of the present approach

Tuning ubiquinone position in biomimetic monolayer membranes

Artificial lipid bilayers have been extensively studied as models that mimic natural membranes (biomimetic membranes). Several attempts of biomimetic membranes inserting ubiquinone (UQ) have been performed to enlighten which the position of UQ in the lipid layer is, although obtaining contradictory results. In this work, pure components (DPPC and UQ) and DPPC:UQ mixtures have been studied using surface pressure-area isotherms and Langmuir-Blodgett (LB) films of the same compounds have been transferred onto solid substrates being topographically characterized on mica using atomic force microscopy and electrochemically on indium tin oxide slides. DPPC:UQ mixtures present less solid-like physical state than pure DPPC indicating a higher-order degree for the latter. UQ influences considerably DPPC during the fluid state, but it is mainly expelled after the phase transition at ˜˜ 26 mN·m^-1 for the 5:1 ratio and at ˜˜ 21 mN·m^-1 for lower UQ content. The thermodynamic studies confirm the stability of the DPPC:UQ mixtures before that event, although presenting a non-ideal behaviour. The results indicate that UQ position can be tuned by means of the surface pressure applied to obtain LB films and the UQ initial content. The UQ positions in the biomimetic membrane are distinguished by their formal potential: UQ located in “diving” position with the UQ placed in the DPPC matrix in direct contact with the electrode surface ( -0.04±0.02 V), inserted between lipid chains without contact to the substrate ( 0.00±0.01 V) and parallel to the substrate, above the lipid chains ( 0.09±0.02 V).Peer ReviewedPostprint (author's final draft

The Phase Behavior of Mixed Lipid Membranes in Presence of the Rippled Phase

We propose a model describing liquid-solid phase coexistence in mixed lipid membranes by including explicitly the occurrence of a rippled phase. For a single component membrane, we employ a previous model in which the membrane thickness is used as an order parameter. As function of temperature, this model properly accounts for the phase behavior of the three possible membrane phases: solid, liquid and the rippled phase. Our primary aim is to explore extensions of this model to binary lipid mixtures by considering the composition dependence of important model parameters. The obtained phase diagrams show various liquid, solid and rippled phase coexistence regions, and are in quantitative agreement with the experimental ones for some specific lipid mixtures.Comment: 8pages, 5figure

Impact of Cholesterol on Voids in Phospholipid Membranes

Free volume pockets or voids are important to many biological processes in cell membranes. Free volume fluctuations are a prerequisite for diffusion of lipids and other macromolecules in lipid bilayers. Permeation of small solutes across a membrane, as well as diffusion of solutes in the membrane interior are further examples of phenomena where voids and their properties play a central role. Cholesterol has been suggested to change the structure and function of membranes by altering their free volume properties. We study the effect of cholesterol on the properties of voids in dipalmitoylphosphatidylcholine (DPPC) bilayers by means of atomistic molecular dynamics simulations. We find that an increasing cholesterol concentration reduces the total amount of free volume in a bilayer. The effect of cholesterol on individual voids is most prominent in the region where the steroid ring structures of cholesterol molecules are located. Here a growing cholesterol content reduces the number of voids, completely removing voids of the size of a cholesterol molecule. The voids also become more elongated. The broad orientational distribution of voids observed in pure DPPC is, with a 30% molar concentration of cholesterol, replaced by a distribution where orientation along the bilayer normal is favored. Our results suggest that instead of being uniformly distributed to the whole bilayer, these effects are localized to the close vicinity of cholesterol molecules

Phase Separation of Saturated and Mono-unsaturated Lipids as determined from a Microscopic Model

A molecular model is proposed of a bilayer consisting of fully saturated DPPC and mono unsaturated DOPC. The model not only encompasses the constant density within the hydrophobic core of the bilayer, but also the tendency of chain segments to align. It is solved within self-consistent field theory. A model bilayer of DPPC undergoes a main chain transition to a gel phase, while a bilayer of DOPC does not do so above zero degrees centigrade because of the double bond which disrupts order. We examine structural and thermodynamic properties of these membranes and find our results in reasonable accord with experiment. In particular, order-parameter profiles are in good agreement with NMR experiments. A phase diagram is obtained for mixtures of these lipids in a membrane at zero tension. The system undergoes phase separation below the main-chain transition temperature of the saturated lipid. Extensions to the ternary DPPC, DOPC, and cholesterol system are outlined.Comment: 29 pages, 4 figures, 1 table. revised versio

Thermodynamic Approach to Phase Coexistence in Ternary Phospholipi-Cholesterol Mixtures

We introduce a simple and predictive model for determining the phase stability of ternary phospholipid-cholesterol mixtures. Assuming that competition between the liquid and gel order of the phospholipids is the main driving force behind lipid segregation, we derive a Gibbs free-energy of mixing, based on the thermodynamic properties of the lipids main transition. A numerical approach was devised that enable the fast and efficient determination of the ternary diagrams associated with our Gibbs free-energy. The computed phase coexistence diagram of DOPC/DPPC/cholesterol reproduces well known features for this system at 10\circ C, as well as its evolution with temperature