Bilayer Properties of Lipid A from Various Gram-Negative Bacteria

Abstract

Lipid A is the lipid anchor of a lipopolysaccharide in the outer leaflet of the outer membrane of Gram-negative bacteria. In general, lipid A consists of two phosphorylated N-acetyl glucosamine and several acyl chains that are directly linked to the two sugars. Depending on the bacterial species and environments, the acyl chain number and length vary, and lipid A can be chemically modified with phosphoethanolamine, aminoarabinose, or glycine residues, which are key to bacterial pathogenesis. In this work, homogeneous lipid bilayers of 21 distinct lipid A types from 12 bacterial species are modeled and simulated to investigate the differences and similarities of their membrane properties. In addition, different neutralizing ion types (Ca 2þ , K þ , and Na þ ) are considered to examine the ion's influence on the membrane properties. The trajectory analysis shows that (1) the area per lipid is mostly correlated to the acyl chain number, and the area per lipid increases as a function of the acyl chain number; (2) the hydrophobic thickness is mainly determined by the average acyl chain length with slight dependence on the acyl chain number, and the hydrophobic thickness generally increases with the average acyl chain length; (3) a good correlation is observed among the area per lipid, hydrophobic thickness, and acyl chain order; and (4) although the influence of neutralizing ion types on the area per lipid and hydrophobic thickness is minimal, Ca 2þ stays longer on the membrane surface than K þ or Na þ , consequently leading to lower lateral diffusion and a higher compressibility modulus, which agrees well with available experiments.

The gram‐negative outer membrane modeler: Automated building of lipopolysaccharide‐rich bacterial outer membranes in four force fields

“…Similarly, PAL5 values (139.17–143.55 Å 2 ) are in agreement with measurements of Lipid A at the liquid crystalline state (125–142 Å 2 ) for P. aeruginosa and other related species . Finally, it should be noted that the simulation results of all Lipid A variants are in agreement with previous simulation evidence for the CHARMM36, MARTINI and GROMOS force fields. Overall, these results show that the Lipid A topologies and simulation systems offered by GNOMM are, in terms of lipid bilayer properties, valid and consistent among different levels of resolution.…”

“…These include variations of Lipid A from four different species ( E. coli , Pseudomonas aeruginosa , Helicobacter pylori and Neisseria meningitidis ) (Supporting Information Fig. S1), as well as three experimentally studied LPSs, containing Lipid A and the oligosaccharide core (Re and Ra LPS for E. coli and PAO1 LPS for P. aeruginosa ) . In addition, a number of standard lipids are also offered, representing the major categories most commonly found in bacteria .…”

“…The recently published CHARMM‐GUI LPS modeler supports the creation of LPSs from various species and their insertion in lipid bilayers through the service's Membrane Builder . However, the LPS modeler is limited to the CHARMM all‐atom force field . Another option is the CHARMM‐GUI Martini Maker, which currently offers two Escherichia coli LPS molecules (Re and Ra LPS) for the MARTINI Coarse‐Grained force field but does not, at present, support any other species.…”

Computer simulations of protein–membrane systems

“…To sum up, the C36 FF allows to accurately represent bilayer properties of fully saturated and monounsaturated lipid molecules in the NpT ensemble. 73 In the last years, different kind of lipids were added to C36 using the same parameter strategy, such as a variety of acyl chains (PUFAs, 123 branched 124 chains and chains with cyclic moieties 125 ) and head groups (PA, PG, PI, and PS), 72,126,127 sterols (cholesterol, 128 ergosterol 129 and plant sterols 130 ), sphingolipids 131 and ceramides 132 as well as glycolipids 133 and LPS 126,134 making use of the CHARMM carbohydrate FF.…”

Progress in Molecular Dynamics Simulations of Gram-Negative Bacterial Cell Envelopes

“…26,27 Im and co-workers provided a comparison of the properties of bilayers composed of several different lipid A types. 28 At the CG level, we are only aware of models of LPS molecules developed within the framework of the popular MARTINI force-field. 14 In one recent study, the ability of pristine fullerenes to penetrate the outer membrane was found to be dependent upon the presence of phospholipids in the outer leaflet as well as the inner leaflet.…”