colfosceril-palmitate and 1-palmitoyl-2-oleoylphosphatidylcholine

Biological membranes have been prominent targets for coarse-grained (CG) molecular dynamics simulations. While minimal CG lipid models with three beads per lipid and quantitative CG lipid models with >10 beads per lipid have been well studied, in between them, CG lipid models with a compatible resolution to residue-level CG protein models are much less developed. Here, we extended a previously developed three-bead lipid model into a five-bead model and parameterized it for two phospholipids, POPC (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine) and DPPC (1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine). The developed model, iSoLF, reproduced the area per lipid, hydrophobic thickness, and phase behaviors of the target phospholipid bilayer membranes at the physiological temperature. The model POPC and DPPC membranes were in liquid and gel phases, respectively, in accordance with experiments. We further examined the spontaneous formation of a membrane bilayer, the temperature dependence of physical properties, the vesicle dynamics, and the POPC/DPPC two-component membrane dynamics of the CG lipid model, showing some promise. Once combined with standard Cα protein models, the iSoLF model will be a powerful tool to simulate large biological membrane systems made of lipids and proteins.

Topics: 1,2-Dipalmitoylphosphatidylcholine; Lipid Bilayers; Membrane Lipids; Membrane Proteins; Models, Chemical; Molecular Dynamics Simulation; Phosphatidylcholines

Cellular membranes containing sphingolipids and cholesterol have been shown to self-organize into lipid rafts-specialized domains that host integral membrane proteins and modulate the bioactivity of cells. In this work, force-distance profiles between raft membranes in the liquid-ordered phase consisting of singly unsaturated 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), a complex mixture of brain sphingomyelin (BSM), and cholesterol were measured using the surface force apparatus (SFA). Two distinct force profiles were detected corresponding to uniform raft membranes and raft membranes with a higher level of topological membrane defects (heterogeneous) as corroborated by atomic force microscopy (AFM) scans. In all cases a weak, long-range electrostatic repulsion was observed with some variation in the surface charge density. The variation in electrostatic repulsion was attributed to charged lipid species primarily from the constituent lipids in the BSM mixture. The adhesion between the uniform raft membranes was comparable to our previous work with pure component, liquid-ordered POPC-DPPC (1,2-dipalmitoyl-sn-glycero-3-phosphocholine)-cholesterol membranes. Raft membranes with more topological defects adhered more strongly owing to hydrophobic attraction between exposed acyl chains. Even though the rafts were in the liquid-ordered phase and membrane defects were present in the contact region, the raft membranes were stable, and no structural rearrangement was observed throughout the measurements. Our findings demonstrate that liquid-ordered membranes are stable to mechanical loading and not particularly sensitive to compositional variation.

Topics: 1,2-Dipalmitoylphosphatidylcholine; Cholesterol; Lipid Bilayers; Membrane Microdomains; Phosphatidylcholines; Sphingomyelins

By reducing the surface tension of the air-water interface in alveoli, lung surfactant (LS) is crucial for proper functioning of the lungs. It also forms the first barrier against inhaled pathogens. In this study we inspect the interactions of LS models with a dangerous air pollutant, benzo[a]pyrene (BaP). Dipalmitoylphosphatidylcholine (DPPC), 1-palmitoyl-2-oleoylphosphatidylcholine, and their 1:1 mixture are used as LS models. Pressure-area isotherms are employed to study macroscopic properties of the monolayers. We find that addition of BaP has a condensing effect, manifested by lowering the values of surface pressure and shifting the isotherms to smaller areas. Atomistic details of this process are examined by means of molecular dynamics simulations. We show that initially BaP molecules are accumulated in the monolayers. Upon compression, they are forced to the headgroups region and eventually expelled to the subphase. BaP presence results in reduction of monolayer hydration in the hydrophilic region. In the hydrophobic region it induces increased chain ordering, reduction of monolayer fluidity, and advances transition to the liquid condensed phase in the DPPC system.

Topics: 1,2-Dipalmitoylphosphatidylcholine; Benzo(a)pyrene; Molecular Dynamics Simulation; Phosphatidylcholines; Pulmonary Alveoli; Pulmonary Surfactants; Surface Tension

The study of the ability of drug molecules to enter cells through the membrane is of vital importance in the field of drug delivery. In cases where the transport of the drug molecules through the membrane is not easily accomplishable, other carrier molecules are used. Spherical fullerene molecules have been postulated as potential carriers of highly hydrophilic drugs across the plasma membrane. Here, we report the coarse-grain molecular dynamics study of the translocation of C60 fullerene and its derivatives across a cell membrane modeled as a 1,2-distearoyl-sn-glycero-3-phosphocholine bilayer. Simulation results indicate that pristine fullerene molecules enter the bilayer quickly and reside within it. The addition of polar functionalized groups makes the fullerenes less likely to reside within the bilayer but increases their residence time in bulk water. Addition of polar functional groups to one half of the fullerene surface, in effect creating a Janus particle, offers the most promise in developing fullerene models that can achieve complete translocation through the membrane bilayer.

Topics: 1,2-Dipalmitoylphosphatidylcholine; Cell Membrane; Fullerenes; Lipid Bilayers; Molecular Dynamics Simulation; Phosphatidylcholines; Temperature

We present a new scheme to estimate the elastic properties of biological membranes in computer simulations. The method analyzes the thermal fluctuations in terms of a coupled undulatory mode, which disentangle the mixing of the mesoscopic undulations and the high-q protrusions. This approach makes possible the accurate estimation of the bending modulus both for membranes under stress and in tensionless conditions; it also extends the applicability of the fluctuation analysis to the small membrane areas normally used in atomistic simulations. Also we clarify the difference between the surface tension imposed in simulations through a pressure coupling barostat, and the surface tension that can be extracted from the analysis of the low wave vector dependence of the coupled undulatory fluctuation spectrum. The physical analysis of the peristaltic mode is also refined, by separating the bulk and protrusions contributions. We illustrate the procedure by analyzing 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine and 1,2-dipalmitoyl-sn-glycero-3-phosphocholine bilayers. The bending moduli obtained from our analysis, shows good agreement with available experiments.

Topics: 1,2-Dipalmitoylphosphatidylcholine; Lipid Bilayers; Molecular Dynamics Simulation; Phosphatidylcholines; Temperature