Does fluoride disrupt hydrogen bond network in cationic lipid bilayer? Time-dependent fluorescence shift of Laurdan and molecular dynamics simulations (original) (raw)
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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.
Structure and interactive properties of highly fluorinated phospholipid bilayers
Biophysical Journal, 1996
Because liposomes containing fluoroalkylated phospholipids are being developed for in vivo drug delivery, the structure and interactive properties of several fluoroalkylated glycerophosphocholines (PCs) were investigated by x-ray diffraction/osmotic stress, dipole potential, and hydrophobic ion binding measurements. The lipids included PCs with highly fluorinated tails on both alkyl chains and PCs with one hydrocarbon chain and one fluoroalkylated chain. Electron density profiles showed high electron density peaks in the center of the bilayer corresponding to the fluorine atoms. The height and width of these high density peaks varied systematically, depending on the number of fluorines and their position on the alkyl chains, and on whether the bilayer was in the gel or liquid crystalline phase. Wide-angle diffraction showed that in both gel and liquid crystalline bilayers the distance between adjacent alkyl chains was greater in fluoroalkylated PCs than in analogous hydrocarbon PCs. For interbilayer separations of less than about 8 A, pressure-distance relations for fluoroalkylated PCs were similar to those previously obtained from PC bilayers with hydrocarbon chains. However, for bilayer separations greater than 8 A, the total repulsive pressure depended on whether the fluoroalkylated PC was in a gel or liquid-crystalline phase. We argue that these pressure-distance relations contain contributions from both hydration and entropic repulsive pressures. Dipole potentials ranged from -680 mV for PCs with both chains fluoroalkylated to -180 mV for PCs with one chain fluoroalkylated, compared to +415 mV for egg PC. The change in dipole potential as a function of subphase concentration of tetraphenylboron was much larger for egg PC than for fluorinated PC monolayers, indicating that the fluorine atoms modified the binding of this hydrophobic anion. Thus, compared to conventional liposomes, liposomes made from fluoroalkylated PCs have different binding properties, which may be relevant to their use as drug carriers.
Biochimica et Biophysica Acta (BBA) - Biomembranes, 2012
16-DSPC … 3-DC 3-DoxylCholestane 5-DSPC … A-ESR angle-resolved electron spin resonance AFD angle-resolved fluorescence depolarization BHT butylated hydroxytoluene DHPE-Bodipy N-(4,4-difluoro-5,7-dimethyl-4-bora-3a,4a-diaza-s-indacene-3-propionyl)-1,2dihexadecanoyl-sn-glycero-3-phosphoethanolamine (triethylammonium salt) DLPC 1,2-dilinoleoyl-sn-glycero-3-phosphocholine DOPC 1,2-dioleoyl-sn-glycero-3-phosphocholine DPH 1,6-diphenyl-1,3,5-hexatriene DPPC FCS fluorescence correlation spectroscopy FRET Förster resonance energy transfer GUV giant unilamellar vesicles HOPLPC
Journal of Physical Chemistry B, 2009
Physicochemical properties of heavy water (D 2 O) differ to some extent from those of normal water. Substituting D 2 O for H 2 O has been shown to affect the structural and dynamic properties of proteins, but studies of its effects on lipid bilayers are scarce. In this paper, the atomic level molecular dynamics (MD) simulation method was used to determine the effects of this substitution on the properties of a dipalmitoylphosphatidylcholine (DPPC) bilayer and its hydrating water. MD simulations of two DPPC bilayers, one fully hydrated with H 2 O and the other with D 2 O, were carried out for over 50 ns. For H 2 O, the simple point charge (SPC) model was used, and for D 2 O, the extended SPC-HW model was employed. Analyses of the simulation trajectories indicate that several properties of the membrane core and the membrane/water interface are affected by replacing H 2 O by D 2 O. However, the time-averaged properties, such as membrane compactness, acyl chain order, and numbers of PC-water H (D)-bonds and PC-PC water bridges, are much less affected than time-resolved properties. In particular, the lifetimes of these interactions are much longer for D 2 O molecules than for H 2 O ones. These longer lifetimes results in a slightly better ordering of the D 2 O molecules and average self-diffusion, which is 50% slower compared with the H 2 O molecules. This large isotope effect has been assigned to the repercussions of the longer lived D-bonding to DPPC headgroups insofar as all water molecules sense the presence of the DPPC bilayer.
Journal of Chemical Theory and Computation, 2010
Molecular dynamics simulations of fully hydrated pure bilayers of four widely studied phospholipids, 1,2-dilauroyl-sn-glycero-3-phosphocholine (DLPC), 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC), 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), and 2-oleoyl-1palmitoyl-sn-glycero-3-phosphocholine (POPC) using a recent revision of the GROMOS96 force field are reported. It is shown that the force field reproduces the structure and the hydration of bilayers formed by each of the four lipids with high accuracy. Specifically, the solvation and the orientation of the dipole of the phosphocholine headgroup and of the ester carbonyls show that the structure of the primary hydration shell in the simulations closely matches experimental findings. This work highlights the need to reproduce a broad range of properties beyond the area per lipid, which is poorly defined experimentally, and to consider the effect of system size and sampling times well beyond those commonly used.
Molecular dynamics investigation of dynamical properties of phosphatidylethanolamine lipid bilayers
The Journal of Chemical Physics, 2005
We describe the dynamic behavior of a 1-stearoyl-2-oleoyl-phosphatidylethanolamine ͑SOPE͒ bilayer from a 20 ns molecular dynamics simulation. The dynamics of individual molecules are characterized in terms of 2 H spin-lattice relaxation rates, nuclear overhauser enhancement spectroscopy ͑NOESY͒ cross-relaxation rates, and lateral diffusion coefficients. Additionally, we describe the dynamics of hydrogen bonding through an analysis of hydrogen bond lifetimes and the time evolution of clusters of hydrogen bonded lipids. The simulated trajectory is shown to be consistent with experimental measures of internal, intermolecular, and diffusive motion. Consistent with our analysis of SOPE structure in the companion paper, we see hydrogen bonding dominating the dynamics of the interface region. Comparison of 2 H T 1 relaxation rates for chain methylene segments in phosphatidylcholine and phosphatidylethanolamine bilayers indicates that slower motion resulting from hydrogen bonding extends at least three carbons into the hydrophobic core. NOESY cross-relaxation rates compare well with experimental values, indicating the observed hydrogen bonding dynamics are realistic. Calculated lateral diffusion rates ͑4±1ϫ 10 −8 cm 2 /s͒ are comparable, though somewhat lower than, those determined by pulsed field gradient NMR methods.
The journal of physical chemistry. B, 2011
Fatty oleic acid (OA) and, recently, its derivative 2-hydroxyoleic acid (2OHOA) have been reported to display an important therapeutic activity. To understand better these therapeutic effects at the molecular and cellular levels, in this work we have carried out molecular dynamics simulations to elucidate the structural and dynamical changes taking place in model 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) and 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) bilayers upon insertion of rising concentrations of these two fatty acids. The simulations are performed using a united-atoms model to describe both the phospholipids and the fatty acids. The process of insertion of the fatty acids from the aqueous phase into the bilayers is simulated first, showing that it is feasible and may lead to some degree of phase separation within the bilayer. The interactions of the embedded homogeneously dispersed fatty acids with the phospholipid chains of the bilayers are then simulated at ...
The dynamics of water at the phospholipid bilayer surface: a molecular dynamics simulation study
Chemical Physics Letters, 2002
Molecular dynamics (MD) simulations of a fully hydrated 1-palmitoyl-2-oleoyl-phosphatidylcholine (POPC) bilayer in the liquid-crystalline state were carried out to investigate the effect of the membrane on the dynamics of water. Translational and rotational motions of water near the membrane surface were restricted. The effect was the strongest for water molecules that were hydrogen (H) bonded to the phosphate (Op) and carbonyl (Oc) oxygen atoms as well as those clathrating choline group of POPC. The translational motion of Oc H bonded water was slower than that of the Op H bonded water, while the rotational motion was faster. Water clatrathing the POPC choline group was less affected than Op and Oc H bonded water. Translational diffusion of all membrane water was faster along the membrane plane than along the membrane normal. Ó
Interactions of monovalent salts with cationic lipid bilayers
Faraday Discussions, 2013
The influence of monovalent salts (NaF, NaCl, NaBr, NaClO 4 , KCl) on the properties of lipid bilayers composed of binary mixtures of zwitterionic DOPC (dioleoylphosphatidylcholine) and cationic DOTAP (dioleoyltrimethylammoniumpropane) is experimentally measured and numerically simulated. Both approaches report a specific adsorption of halide anions at the cationic bilayer. The adsorption is enhanced for higher content of DOTAP in DOPC/DOTAP mixtures and for larger anions (Br À and ClO 4 À ). The nonmonotonic dependence of the lipid headgroup mobility, determined using time-dependent fluorescence shifts of Laurdan located at the bilayer carbonyl level, on the content of cationic lipid is preserved in all examined salt solutions. Its maximum, however, is shifted towards higher DOTAP concentrations in the row: NaF < NaCl < NaBr. The same ordering of salts is found for the simulated area per lipid and the measured rigidification of pure DOTAP bilayers. Simulations reveal that Br À strongly binds to the cationic headgroups of DOTAP neutralising the bilayer, which induces lateral inhomogeneities in the form of hydrophilic and hydrophobic patches at the membrane-water interface for pure DOTAP. In the equimolar DOPC/DOTAP mixture the neutralising effect of Br À results in bending of the PC headgroups to a bilayer-parallel orientation. F À , while attracted to the DOTAP bilayer, has an opposite effect to that of Br À , i.e. it increases local mobility at the lipid carbonyl level. We attribute this effect to the disruption of the hydrogen-bonded structure of the molecules of lipids and water caused by the presence of the adsorbed F À .