Structure of lipid bilayers

This paper describes the parametrization of a new coarse grained (CG) model for lipid and surfactant systems. Reduction of the number of degrees of freedom together with the use of short range potentials makes it computationally very efficient. Compared to atomistic models a gain of 3-4 orders of magnitude can be achieved. Micrometer length scales or millisecond time scales are therefore within reach. To encourage applications, the model is kept very simple. Only a small number of coarse grained atom types are defined, which interact using a few discrete levels of interaction. Despite the computational speed and the simplistic nature of the model, it proves to be both versatile in its applications and accurate in its predictions. We show that densities of liquid alkanes from decane up to eicosane can be reproduced to within 5%, and the mutual solubilities of alkanes in water and water in alkanes can be reproduced within 0.5 kT of the experimental values. The CG model for dipalmitoylphosphatidylcholine (DPPC) is shown to aggregate spontaneously into a bilayer. Structural properties such as the area per headgroup and the phosphate-phosphate distance match the experimentally measured quantities closely. The same is true for elastic properties such as the bending modulus and the area compressibility, and dynamic properties such as the lipid lateral diffusion coefficient and the water permeation rate. The distribution of the individual lipid components along the bilayer normal is very similar to distributions obtained from atomistic simulations. Phospholipids with different headgroup (ethanolamine) or different tail lengths (lauroyl, stearoyl) or unsaturated tails (oleoyl) can also be modeled with the CG force field. The experimental area per headgroup can be reproduced for most lipids within 0.02 nm(2). Finally, the CG model is applied to nonbilayer phases. Dodecylphosphocholine (DPC) aggregates into small micelles that are structurally very similar to ones modeled atomistically, and DOPE forms an inverted hexagonal phase with structural parameters in agreement with experimental data.

/pdf/coarse-grained-model-for-semiquantitative-lipid-simulations-3235leilrn.pdf

Coarse grained model for semiquantitative lipid simulations

The AMBER lipid force field has been updated to create Lipid14, allowing tensionless simulation of a number of lipid types with the AMBER MD package. The modular nature of this force field allows numerous combinations of head and tail groups to create different lipid types, enabling the easy insertion of new lipid species. The Lennard-Jones and torsion parameters of both the head and tail groups have been revised and updated partial charges calculated. The force field has been validated by simulating bilayers of six different lipid types for a total of 0.5 μs each without applying a surface tension; with favorable comparison to experiment for properties such as area per lipid, volume per lipid, bilayer thickness, NMR order parameters, scattering data, and lipid lateral diffusion. As the derivation of this force field is consistent with the AMBER development philosophy, Lipid14 is compatible with the AMBER protein, nucleic acid, carbohydrate, and small molecule force fields.

/pdf/lipid14-the-amber-lipid-force-field-1gj0t3c4bx.pdf

Lipid14: The Amber Lipid Force Field

Phospholipids play multiple roles in cells by establishing the permeability barrier for cells and cell organelles, by providing the matrix for the assembly and function of a wide variety of catalytic processes, by acting as donors in the synthesis of macromolecules, and by actively influencing the functional properties of membrane-associated processes. The function, at the molecular level, of phosphatidylethanolamine, phosphatidylglycerol, and cardiolipin in specific cellular processes is reviewed, with a focus on the results of combined molecular genetic and biochemical studies in Escherichia coli. These results are compared with primarily biochemical data supporting similar functions for these phospholipids in eukaryotic organisms. The wide range of processes in which specific involvement of phospholipids has been documented explains the need for diversity in phospholipid structure and why there are so many membrane lipids.

MOLECULAR BASIS FOR MEMBRANE PHOSPHOLIPID DIVERSITY: Why Are There So Many Lipids?

http://norbbi.com/public/publications/Kucerka_BBA(2011).pdf

Fluid Phase Lipid Areas and Bilayer Thicknesses of Commonly Used Phosphatidylcholines as a Function of Temperature

Area per Lipid and Acyl Length Distributions in Fluid Phosphatidylcholines Determined by 2H NMR Spectroscopy

Molecular areas of phospholipids as determined by 2H NMR spectroscopy. Comparison of phosphatidylethanolamines and phosphatidylcholines

The gain a better understanding of the biological roles of polyunsaturated phospholipids, deuterium (/sup 2/H) NMR studies have been conducted of 1-perdeuteriopalmitoyl-2-docosahexaenoyl-sn-glycero-3-phosphocholine, an asymmetric or mixed-chain saturated-polyunsaturated phospholipid, in the liquid crystalline (L/sub ..cap alpha../) phase. The palmitoyl (16:0) chain at the glycerol sn-1 position was labeled with /sup 2/H by perdeuteration, whereas the polyunsaturated, docosahexaenoyl (22:6 omega 3) chain at the sn-2 position was unlabeled, i.e., protiated. The /sup 2/H NMR results were compared to studies of 1,2-diperdeuteriopalmitoyl-sn-glycero-3-phosphocholine, in which both the sn-1 and sn-2 palmitoyl chains were perdeuterated, as well as 1-palmitoyl-2-perdeuteriopalmitoyl-sn-glycero-3-phosphocholine, in which only the sn-2 chain was perdeuterated. Multilamellar phospholipid dispersions containing 50 wt % H/sub 2/O were employed, and /sup 2/H NMR spectra were obtained using quadrupolar echo methods at a magnetic field strength of 8.5 T. The experimental /sup 2/H NMR spectra were numerically deconvoluted (de-Paked) to yield subspectra corresponding to the parallel bilayer orientation with respect to the main applied magnetic field. The increased resolution of the de-Paked subspectra enabled profiles of the segmental order parameters of the individual C-/sup 2/H bonds, denoted by absolute value of S/sub CD/(i), to be derived as a function of chain position. Significant differences in the /supmore » 2/H NMR spectra and derived absolute value of S/sub CD/(i) profiles of the per-/sup 2/H-16:0 chains of the polyunsaturated and saturated bilayers were found.« less

Configurational statistics of acyl chains in polyunsaturated lipid bilayers from deuterium nmr

In deuterium (2H) NMR spectroscopy of fluid lipid bilayers, the average structure is manifested in the segmental order parameters (SCD) of the flexible molecules. The corresponding spin−lattice relaxation rates (R1Z) depend on both the amplitudes and the rates of the segmental fluctuations, and indicate the types of lipid motions. By combining 2H NMR order parameter measurements with relaxation studies, we have obtained a more comprehensive picture of lipids in the liquid-crystalline (Lα) state than formerly possible. Our data suggest that a lipid bilayer constitutes an ordered fluid, in which the phospholipids are grafted to the aqueous interface via their polar headgroups, whereas the fatty acyl chains are in effect liquid hydrocarbon. Studies of 2H-labeled saturated lipids indicate their R1Z rates and SCD order parameters are correlated by a model-free, square-law functional dependence, signifying the presence of relatively slow bilayer fluctuations. A new composite membrane deformation model explains ...

Elastic deformation of membrane bilayers probed by deuterium NMR relaxation.

PACS number~s!: 87.16.2b, 76.60.2k, 87.64.Hd The properties of flexible amphiphilic layers composed of phospholipids are of fundamental interest to physicists with regard to their microstructures @1‐5#, and play a role in key biological functions @6#. These and other fascinating soft materials can be studied using nuclear spin-lattice relaxation ~for reviews, see Refs. @7,8#!. In this Rapid Communication, we report NMR relaxation data that provide knowledge of the viscoelastic properties of lipid bilayers, including their dependence on composition. The results imply that the concept of elastic deformation of membranes is applicable on the mesoscopic length scale, approaching the molecular dimensions, with quasicoherent modes on the order of the bilayer hydrocarbon thickness and less @9#. We suggest the entire spectrum of fluctuations is important for repulsions due to entropic confinement, including long wavelength undulations as well as higher frequency excitations.

Steven W. Dodd

Papers

Area per Lipid and Acyl Length Distributions in Fluid Phosphatidylcholines Determined by 2H NMR Spectroscopy

Molecular areas of phospholipids as determined by 2H NMR spectroscopy. Comparison of phosphatidylethanolamines and phosphatidylcholines

Configurational statistics of acyl chains in polyunsaturated lipid bilayers from deuterium nmr

Elastic deformation of membrane bilayers probed by deuterium NMR relaxation.

Composite membrane deformation on the mesoscopic length scale.