Rigidification of Neutral Lipid Bilayers in the Presence of Salts

Pabst, Georg; Hodžić, Aden; Štrancar, Janez; Danner, Sabine; Rappolt, Michael; Laggner, Peter

doi:10.1529/biophysj.107.112615

Cited by 213 publications

(282 citation statements)

References 63 publications

(114 reference statements)

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“…As we 70 and others 65,67,76,77 have recently demonstrated, small cations such as Na + bind to the ester/carbonyl atoms of phospholipids, inducing a slight enhancement of the lipid order (whereas common counter ions such as Cl À remain firmly in the aqueous phase and do not affect the lipids). Although we have not included ions in these simulations, we expect that the addition of a salt such as NaCl would lead to a systematic ordering effect, identical for all sterols along the series, and therefore all comparative conclusions of this study would be unchanged.…”

Section: View Article Onlinementioning

confidence: 70%

Influence of the sterol aliphatic side chain on membrane properties: a molecular dynamics study

Robalo

Ramalho

Huster

et al. 2015

Phys. Chem. Chem. Phys.

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Following a recent experimental investigation of the effect of the length of the alkyl side chain in a series of cholesterol analogues (Angew. Chem., Int. Ed., 2013, 52, 12848-12851), we report here an atomistic molecular dynamics characterization of the behaviour of methyl-branched side chain sterols (iso series) in POPC bilayers. The studied sterols included androstenol (i-C0-sterol) and cholesterol (i-C8-sterol), as well as four other derivatives (i-C5, i-C10, i-C12 and i-C14-sterol). For each sterol, both subtle local effects and more substantial differential alterations of membrane properties along the iso series were investigated. The location and orientation of the tetracyclic ring system is almost identical in all compounds. Among all the studied sterols, cholesterol is the sterol that presents the best matching with the hydrophobic length of POPC acyl chains, whereas longer-chained sterols interdigitate into the opposing membrane leaflet. In accordance with the experimental observations, a maximal ordering effect is observed for intermediate sterol chain length (i-C5, cholesterol, i-C10). Only for these sterols a preferential interaction with the saturated sn-1 chain of POPC (compared to the unsaturated sn-2 chain) was observed, but not for either shorter or longer-chained derivatives. This work highlights the importance of the sterol alkyl chain in the modulation of membrane properties and lateral organization in biological membranes.

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Section: View Article Onlinementioning

confidence: 70%

Influence of the sterol aliphatic side chain on membrane properties: a molecular dynamics study

Robalo

Ramalho

Huster

et al. 2015

Phys. Chem. Chem. Phys.

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“…28,30 During the past decade, however, this view has been challenged. Indirect evidence from infrared spectroscopy, 32 fluorescence correlation spectroscopy, 33 atomic force microscopy, 35,36 smallangle X-ray diffraction, 41 spin-labeling electron paramagnetic resonance spectroscopy, 41 and calorimetric 33,41 studies suggest the possibility of Na + interacting with lipid carbonyl oxygens, binding lipids into complexes, and thus leading to detectable changes in area per lipid, bilayer thickness and rigidity, 41 as Hopping greatly promoted the lateral diffusion of Na + within the carbonyl region. The lateral mean squared displacement (MSD) of sodiums continuously complexed with DMPC (thick dashed red line) is considerably smaller than if lipid-free hops are allowed (thick continuous black).…”

Section: Discussionmentioning

confidence: 99%

“…Experiments have shown that anionic 4, [22][23][24][25] and cationic 26,27 membranes interact readily with their counterions (especially divalent ones), whereas the interactions of zwitterionic lipid bilayers with salt ions appear rather sensitive to the size and valency of ions. [28][29][30][31][32][33][34][35][36][37][38][39][40][41] As for molecular-level computational studies, the increase in computing power in the past few years has made it possible to extend computer simulations beyond the relatively long relaxation times of tens to hundreds of nanoseconds required for equilibration of ions in lipid/water systems. Although most computational studies by far have focused on the effects of salt ions on zwitterionic (neutral) lipid bilayers, 33,[42][43][44][45][46][47][48][49][50][51][52][53] there is also an increasing number of studies on anionic [54][55][56][57][58][59] and cationic 60,61 lipid bilayers.…”

Section: Introductionmentioning

confidence: 99%

Ion Dynamics in Cationic Lipid Bilayer Systems in Saline Solutions

et al. 2009

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Positively charged lipid bilayer systems are a promising class of nonviral vectors for safe and efficient gene and drug delivery. Detailed understanding of these systems is therefore not only of fundamental but also of practical biomedical interest. Here, we study bilayers comprising a binary mixture of cationic dimyristoyltrimethylammoniumpropane (DMTAP) and zwitterionic (neutral) dimyristoylphosphatidylcholine (DMPC) lipids. Using atomistic molecular dynamics simulations, we address the effects of bilayer composition (cationic to zwitterionic lipid fraction) and of NaCl electrolyte concentration on the dynamical properties of these cationic lipid bilayer systems. We find that, despite the fact that DMPCs form complexes via Na + ions that bind to the lipid carbonyl oxygens, NaCl concentration has a rather minute effect on lipid diffusion. We also find the dynamics of Cl -and Na + ions at the water-membrane interface to differ qualitatively. Cl -ions have well-defined characteristic residence times of nanosecond scale. In contrast, the binding of Na + ions to the carbonyl region appears to lack a characteristic time scale, as the residence time distributions displayed power-law features. As to lateral dynamics, the diffusion of Na + ions within the water-membrane interface consists of two qualitatively different modes of motion: very slow diffusion when ions are bound to DMPC, punctuated by fast rapid jumps when detached from the lipids. Overall, the prolonged dynamics of the Na + ions are concluded to be interesting for the physics of the whole membrane, especially considering its interaction dynamics with charged macromolecular surfaces.

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“…Increases in the order of POPC acyl chains in the presence of NaCl have been described both experimentally 74 and by MD simulations. 60,62,75 These MD studies showed that the chloride ion has an external distribution, with a maximum clearly outside that of the POPC head group atoms, and probably has little if any impact on acyl View Article Online chain order.…”

Section: View Article Onlinementioning

confidence: 99%

Behaviour of NBD-head group labelled phosphatidylethanolamines in POPC bilayers: a molecular dynamics study

Filipe

Santos

Ramalho

et al. 2015

Phys. Chem. Chem. Phys.

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A complete homologous series of fluorescent phosphatidylethanolamines (diC n PE), labelled at the head group with a 7-nitrobenz-2-oxa-1,3-diazo-4-yl(NBD) fluorophore and inserted in 1-palmitoyl, 2-oleoyl-snglycero-3-phosphocholine (POPC) bilayers, was studied using atomistic molecular dynamics simulations. The longer-chained derivatives of NBD-diC n PE, with n = 14, 16, and 18, are commercially available, and widely used as fluorescent membrane probes. Properties such as location of atomic groups and acyl chain order parameters of both POPC and NBD-diC n PE, fluorophore orientation and hydrogen bonding, membrane electrostatic potential and lateral diffusion were calculated for all derivatives in the series. Most of these probes induce local disordering of POPC acyl chains, which is on the whole counterbalanced by ordering resulting from binding of sodium ions to lipid carbonyl/glycerol oxygen atoms. An exception is found for NBD-diC 16 PE, which displays optimal matching with POPC acyl chain length and induces a slight local ordering of phospholipid acyl chains. Compared to previously studied fatty amines, acyl chain-labelled phosphatidylcholines, and sterols bearing the same fluorescent tag, the chromophore in NBD-diC n PE locates in a similar region of the membrane (near the glycerol backbone/carbonyl region) but adopts a different orientation (with the NO 2 group facing the interior of the bilayer). This modification leads to an inverted orientation of the P-N axis in the labelled lipid, which affects the interface properties, such as the membrane electrostatic potential and hydrogen bonding to lipid head group atoms. The implications of this study for the interpretation of the photophysical properties of NBD-diC n PE (complex fluorescence emission kinetics, differences with other NBD lipid probes) are discussed.

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Rigidification of Neutral Lipid Bilayers in the Presence of Salts

Cited by 213 publications

References 63 publications

Influence of the sterol aliphatic side chain on membrane properties: a molecular dynamics study

Influence of the sterol aliphatic side chain on membrane properties: a molecular dynamics study

Ion Dynamics in Cationic Lipid Bilayer Systems in Saline Solutions

Behaviour of NBD-head group labelled phosphatidylethanolamines in POPC bilayers: a molecular dynamics study

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