A Molecular Dynamics Study of the Response of Lipid Bilayers and Monolayers to Trehalose (original) (raw)
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Biophysical Journal, 1995
In this paper we report on the molecular dynamics simulation of a fluid phase hydrated dimyristoylphosphatidylcholine bilayer. The initial configuration of the lipid was the x-ray crystal structure. A distinctive feature of this simulation is that, upon heating the system, the fluid phase emerged from parameters, initial conditions, and boundary conditions determined independently of the collective properties of the fluid phase. The initial conditions did not include chain disorder characteristic of the fluid phase. The partial charges on the lipids were determined by ab initio self-consistent field calculations and required no adjustment to produce a fluid phase. The boundary conditions were constant pressure and temperature. Thus the membrane was not explicitly required to assume an area/phospholipid molecule thought to be characteristic of the fluid phase, as is the case in constant volume simulations. Normal to the membrane plane, the pressure was 1 atmosphere, corresponding to the normal laboratory situation. Parallel to the membrane plane a negative pressure of -100 atmospheres was applied, derived from the measured surface tension of a monolayer at an air-water interface. The measured features of the computed membrane are generally in close agreement with experiment. Our results confirm the concept that, for appropriately matched temperature and surface pressure, a monolayer is a close approximation to one-half of a bilayer. Our results suggest that the surface area per phospholipid molecule for fluid phosphatidylcholine bilayer membranes is smaller than has generally been assumed in computational studies at constant volume. Our results confirm that the basis of the measured dipole potential is primarily water orientations and also suggest the presence of potential barriers for the movement of positive charges across the water-headgroup interfacial region of the phospholipid.
Interaction of the Disaccharide Trehalose with a Phospholipid Bilayer: A Molecular Dynamics Study
Biophysical Journal, 2004
The disaccharide trehalose is well known for its bioprotective properties. Produced in large amounts during stress periods in the life of organisms able to survive potentially damaging conditions, trehalose plays its protective role by stabilizing biostructures such as proteins and lipid membranes. In this study, molecular dynamics simulations are used to investigate the interaction of trehalose with a phospholipid bilayer at atomistic resolution. Simulations of the bilayer in the absence and in the presence of trehalose at two different concentrations (1 or 2 molal) are carried out at 325 K and 475 K. The results show that trehalose is able to minimize the disruptive effect of the elevated temperature and stabilize the bilayer structure. At both temperature, trehalose is found to interact directly with the bilayer through hydrogen bonds. However, the water molecules at the bilayer surface are not completely replaced. At high temperature, the protective effect of trehalose is correlated with a significant increase in the number of trehalose-bilayer hydrogen bonds, predominantly through an increase in the number of trehalose molecules bridging three or more lipid molecules.
Modulating Membrane Properties: The Effect of Trehalose and Cholesterol on a Phospholipid Bilayer
The Journal of Physical Chemistry B, 2005
The protective properties of trehalose on cholesterol-containing lipid dipalmitoylphosphatidylcholine (DPPC) bilayers are studied through molecular simulations. The ability of the disaccharide to interact with the phospholipid headgroups and stabilize the membrane persists even at high cholesterol concentrations and restricts some of the changes to the structure that would otherwise be imposed by cholesterol molecules. Predictions of bilayer properties such as area per lipid, tail ordering, and chain conformation support the notion that the disaccharide decreases the main melting transition in these multicomponent model membranes, which correspond more closely to common biological systems than pure bilayers. Molecular simulations indicate that the membrane dynamics are slowed considerably by the presence of trehalose, indicating that high sugar concentrations would serve to avert possible phase separations that could arise in mixed phospholipid systems. Various time correlation functions suggest that the character of the modifications in lipid dynamics induced by trehalose and cholesterol is different in the hydrophilic and hydrophobic regions of the membrane.
The Journal of Chemical Physics, 2000
The spatial and groupwise distribution of surface tension in a fully hydrated 256 lipid dipalmitoylphosphatidylcholine ͑DPPC͒ bilayer is determined from a 5 ns molecular dynamics simulation by resolving the normal and lateral pressures in space through the introduction of a local virial. The resulting surface tension is separated into contributions from different types of interactions and pairwise terms between lipid headgroups, chains and water. By additionally performing a series of five simulations at constant areas ranging from 0.605 to 0.665 nm 2 ͑each of 6 ns length͒, it is possible to independently resolve the energetic contributions to surface tension from the area dependence of the interaction energies. This also enables us to calculate the remaining entropic part of the tension and the thermal expansivity. Together with the total lateral pressures this yields a full decomposition of surface tension into energetic and entropic contributions from electrostatics, Lennard-Jones and bonded interactions between lipid chains, headgroups and water molecules. The resulting total surface tension in the bilayer is found to be a sum of very large terms of opposing signs, explaining the sensitivity of simulation surface tension to details in force fields. Headgroup and headgroup-water interactions are identified as attractive on average while the chain region wants to expand the bilayer. Both effects are dominated by entropic contributions but there are also substantial energetic terms in the hydrophobic core. The net lateral pressure is small and relatively smooth compared to the individual components, in agreement with experimental observations of DPPC lipids forming stable bilayers.
Effect of Trehalose on a Phospholipid Membrane under Mechanical Stress
Biophysical Journal, 2008
Explicit solvent molecular dynamics simulations were used to investigate at atomic resolution the effect of trehalose on a hydrated phospholipid bilayer under mechanical stress (stretching forces imposed in the form of negative lateral pressure). Simulations were performed in the absence or presence of trehalose at 325 K, and with different values for negative lateral pressure. In the concentration regime (2 molal) and range of lateral pressures (1 to À250 bar) investigated, trehalose was found to interact directly with the membrane, partially replacing water molecules in the formation of hydrogen bonds with the lipid headgroups. Similar to previous findings in the context of thermal stress, the number, degree of bridging, and reaching depth of these hydrogen bonds increased with the magnitude of perturbation. However, at the concentration considered, trehalose was not sufficient to preserve the integrity of the membrane structure and to prevent its extreme elongation (and possible disruption) under the effect of stretching forces.
2020
The spatial and groupwise distribution of surface tension in a fully hydrated 256 lipid dipalmitoylphosphatidylcholine ͑DPPC͒ bilayer is determined from a 5 ns molecular dynamics simulation by resolving the normal and lateral pressures in space through the introduction of a local virial. The resulting surface tension is separated into contributions from different types of interactions and pairwise terms between lipid headgroups, chains and water. By additionally performing a series of five simulations at constant areas ranging from 0.605 to 0.665 nm 2 ͑each of 6 ns length͒, it is possible to independently resolve the energetic contributions to surface tension from the area dependence of the interaction energies. This also enables us to calculate the remaining entropic part of the tension and the thermal expansivity. Together with the total lateral pressures this yields a full decomposition of surface tension into energetic and entropic contributions from electrostatics, Lennard-Jone...
The Journal of Physical Chemistry B, 2004
An analysis of the structural and dynamical hydrogen bonding interactions at the lipid water interface from a 10 ns molecular dynamics simulation of a hydrated dimyristoylphosphatidylcholine (DMPC) lipid bilayer is presented. We find that the average number of hydrogen bonds per lipid oxygen atom varies depending on its position within the lipid. Radial distribution functions are reported for water interacting with lipid oxygen, nitrogen, and phosphorus atoms, as well as for lipid-lipid interactions. The extent of inter-and intramolecular lipid-water-lipid hydrogen bond bridges is explored along with charge pair associations among headgroups of different lipid molecules. We also examine the hydrogen bonding dynamics of water at the lipid surface. A picture emerges of a sticky interface where water that is hydrogen bonded to lipid oxygen atoms diffuses slowly. Hydrogen bonds between water and the double bonded lipid oxygen atoms are longer lived than those to single bonded lipid oxygen atoms, and hydrogen bonds between water and the tail lipid oxygen atoms are longer lived than those to headgroup oxygen atoms. The implications of these results for lateral proton transfer at the interface are also discussed.
European Biophysics Journal, 2005
Trehalose is a sugar which plays an important protectant role in organisms against damage due to dehydration. To explore the basic molecular mechanism which governs the protective function exerted on lipid membranes, X-ray diffraction and osmotic stress experiments have been performed on L-a-dioleoylphosphatidyl-ethanolamine (DOPE) in trehalose solutions of different concentrations. In pure water, DOPE forms an inverted hexagonal (H II ) phase; in sugar solutions, a strong dehydration, which induces a large reduction of the H II lattice parameter, has been detected, but nevertheless no phase transitions occur. Structural data, directly obtained from reconstructed electron density maps, show that the bending of the lipid monolayer induced by the sugar is coupled to changes in the DOPE molecular shape. By osmotic stress, the work required to dehydrate the monolayer has been obtained and the overall free energy described as a function of trehalose concentration. Three results should be stressed: (1) dehydration experiments performed in the presence of sugar demonstrate that the protective effect cannot be purely osmotic; (2) the pivotal surface, that location on the molecule whose area is invariant upon isothermal bending, has been analyzed by two different methods: the approach by Rand and co-workers and the approach by Templer and co-workers; in both cases its presence along the DOPE molecule has been revealed and its position estimated; (3) the spontaneous radius of curvature and the rigidity constant of the lipid monolayer, measured at the pivotal plane, changes from 3.06 nm (in pure water) to 2.82 nm (in 1.4 M trehalose), and from 0.55·10 À19 to 0.74·10 À19 J, respectively. We assume that these modifications are related to direct interactions between trehalose and DOPE that alter the interface geometry, reducing the repulsion between the polar heads. However, the increased bending rigidity also accounts for the changes of the property of the aqueous compartment, reflecting the rigidity and stiffness of the sugar matrix around and inside the lipid phase.
Cryobiology, 1988
Dipalmitoylphosphatidylcholine (DPPC) bilayers hydrated in the presence of trehalose were equilibrated at various temperatures (4, 20, and 60 degrees C) corresponding to the crystalline Lc, gel L beta', and liquid-crystalline L alpha phases, respectively, and then desiccated at these temperatures or freeze-dried at -80 degrees C to ca. DPPC dihydrate. The thermotropic behavior of the resulting DPPC/trehalose mixtures was investigated by differential scanning calorimetry and found to be dependent not only on the trehalose concentration but also on the phase state of the hydrated bilayers prior to their drying. Trehalose was most effective when the desiccation was carried out from the L alpha phase at 60 degrees C. In this case, one trehalose molecule per two DPPC molecules was sufficient to depress the melting temperature from values typical of DPPC dihydrate to 45 degrees C. Trehalose's influence decreased when dried from the L beta' phase and was significantly less pronounced when dried from the Lc phase. These data show that trehalose's protective influence depends on the initial phase state of the lipid bilayer and reaches its maximum in the liquid-crystalline state. The possible role of this effect in anhydrobiosis is pointed out.