Effects of the Nonimmobilizer Hexafluroethane on the Model Membrane Dimyristoylphosphatidylcholine

2002 ◽  
Vol 97 (4) ◽  
pp. 848-855 ◽  
Author(s):  
Laure Koubi ◽  
Mounir Tarek ◽  
Sanjoy Bandyopadhyay ◽  
Michael L. Klein ◽  
Daphna Scharf
Keyword(s):  
Physical Properties ◽  
Lipid Bilayer ◽  
Md Simulations ◽  
Model Membrane ◽  
Head Group ◽  
Clinical Effects ◽  
Equilibrium Configurations ◽  
Area Per Lipid ◽  
Lipid Head Group ◽  
Chain Conformations

Background Nonimmobilizers are agents that lack anesthetic properties, although their chemical structure is very similar to known anesthetics. The primary action site of both agents, whether at the membrane or target protein level, is still a matter of debate. However, increasing evidence points to the distinct modifications of the membrane physical properties that such agents induce. Such modification may play a role in the mechanism of anesthesia, and may therefore be related to the differences in their clinical behavior. Methods Molecular dynamics (MD) computer simulations have been used to investigate the distribution of a nonimmobilizer, hexafluroethane (HFE, C(2)F(6)), in a lipid membrane. The biologically relevant liquid-crystal phase of a hydrated dimyristoyl phosphatidyl choline (DMPC) bilayer was used as a membrane model. Two MD simulations corresponding to HFE mole fractions of 6% and 25% have been performed at room temperature and constant ambient pressure, for a duration of 2 nanoseconds each. Results The equilibrium configurations of HFE in the bilayer show that the nonimmobilizer molecules are evenly distributed along the lipid hydrocarbon chains with a slight preference for the bilayer center. This partitioning induces an expansion of the bilayer thickness and a lateral contraction of the membrane (decrease of the area per lipid). The presence of HFE has essentially no effect on the lipid acyl chain conformations in agreement with nuclear magnetic resonance (NMR) measurements of the chain order parameters. The partitioning of the nonimmobilizer does not influence the orientation of the lipid head-group dipole moment. Conclusions The modifications induced by the presence of the nonimmobilizer HFE on a model membrane are distinct from those previously found for halothane (CF(3)CHBrCl), its anesthetic analogue, and appear to result from different distributions in the lipid bilayer. The results of the MD simulations show that (1) the changes in the average area per lipid and in the membrane thickness are opposite for the two agents and (2) HFE induces no change in the lipid head-group orientation, in contrast to halothane. These different effects (1) on the physical properties of the lipid bilayer and (2) on the electrostatic properties of the membrane-water interface may be linked to different clinical effects, and thus might contribute to the mechanism of general anesthesia.

scholarly journals Influenza A M2 Spans the Membrane Bilayer, Perturbs its Organization and Differentiates the Effect of Amantadine and Spiro[pyrrolidine-2,2'-adamantane] AK13 on Lipids

2019 ◽  
Author(s):  
Athina Konstantinidi ◽  
Maria Chountoulesi ◽  
Nikolaos Naziris ◽  
Barbara Sartori ◽  
Heinz Amenitsch ◽  
...  
Keyword(s):  
Influenza A ◽  
Acyl Chain ◽  
Md Simulations ◽  
Head Group ◽  
Ammonium Group ◽  
Drug Molecules ◽  
Carboxylate Groups ◽  
Head Surface ◽  
Lipid Head Group ◽  
Phosphate Groups

The investigation and observations made for the M2TM, excess aminoadamantane ligands in DMPC were made using the simpler version of biophysical methods including SDC, SAXS and WAXS, MD simulations and ssNMR. 1H, 31P ssNMR and MD simulations, showed that M2TM in apo form or drug-bound form span the membrane interacting strongly with lipid acyl chain tails and the phosphate groups of the polar head surface. The MD simulations showed that the drugs anchor through their ammonium group with the lipid phosphate and occasionally with M2TM asparagine-44 carboxylate groups. The 13C ssNMR experiments allow the inspection of excess drug molecules and the assessment of its impact on the lipid head-group region. At low peptide concentrations of influenza A M2TM tetramer in DPMC bilayer, two lipid domains were observed that likely correspond to the M2TM boundary lipids and the bulk-like lipids. At high peptide concentrations, one domain was identified which constitute essentially all of the lipids which behave as boundary. This effect is likely due, according to the MD simulations, to the preference of AK13 to locate in closer vicinity to M2TM compared to Amt as well as the stronger ionic interactions of Amt primary ammonium group with phosphate groups, compared with the secondary buried ammonium group in AK13.<br>

scholarly journals Structural Effects of Cation Binding to DPPC Monolayers

2020 ◽  
Author(s):  
Matti Javanainen ◽  
Wei Hua ◽  
Ondrej Tichacek ◽  
Pauline Delcroix ◽  
Lukasz Cwiklik ◽  
...  
Keyword(s):  
Radical Change ◽  
Binding Mode ◽  
Cation Binding ◽  
Head Group ◽  
Binding Modes ◽  
Sum Frequency ◽  
Area Per Lipid ◽  
Simulation And Experiment ◽  
Lipid Head Group ◽  
Dynamics Simulations

Ions at the two sides of the plasma membrane maintain the transmembrane potential, participate in signaling, and affect the properties of the membrane itself. The extracellular leaflet is particularly enriched in phosphatidylcholine lipids an under the influence of Na+, Ca2+, and Cl− ions. In this work, we combined molecular dynamics simulations performed using state-of-the-art models with vibrational sum frequency generation (VSFG) spectroscopy to study the effects of these key ions on the structure of dipalmitoylphosphatidylcholine. We used lipid monolayers as a proxy for membranes, as this approach enabled a direct comparison between simulation and experiment. We find that the effects of Na+ are minor. Ca2+, on the other hand, strongly affects the lipid head group conformations and induces a tighter packing of lipids, thus promoting the liquid condensed phase. It does so by binding to both the phosphate and carbonyl oxygens via direct and water-mediated binding modes, the ratios of which depend on the monolayer packing. Clustering analysis performed on simulation data revealed that changes in area per lipid or CaCl2 concentration both affect the head group conformations, yet their effects are anti-correlated. Cations at the monolayer surface also attract Cl−, which at large CaCl2 concentrations penetrates deep to the monolayer. This phenomenon coincides with a radical change in the VSFG spectra of the phosphate group, thus indicating the emergence of a new binding mode.

Influence of isoform-specific Ras lipidation motifs on protein partitioning and dynamics in model membrane systems of various complexity

2017 ◽  
Vol 398 (5-6) ◽  
pp. 547-563 ◽  
Author(s):  
Nelli Erwin ◽  
Satyajit Patra ◽  
Mridula Dwivedi ◽  
Katrin Weise ◽  
Roland Winter
Keyword(s):  
Dynamic Properties ◽  
Group Structure ◽  
Model Membrane ◽  
Head Group ◽  
Membrane Systems ◽  
Biophysical Approach ◽  
Lipid Head Group ◽  
Fluid Bilayers ◽  
Binary Fluid Mixtures ◽  
Protein Rich

Abstract The partitioning of the lipidated signaling proteins N-Ras and K-Ras4B into various membrane systems, ranging from single-component fluid bilayers, binary fluid mixtures, heterogeneous raft model membranes up to complex native-like lipid mixtures (GPMVs) in the absence and presence of integral membrane proteins have been explored in the last decade in a combined chemical-biological and biophysical approach. These studies have revealed pronounced isoform-specific differences regarding the lateral distribution in membranes and formation of protein-rich membrane domains. In this context, we will also discuss the effects of lipid head group structure and charge density on the partitioning behavior of the lipoproteins. Moreover, the dynamic properties of N-Ras and K-Ras4B have been studied in different model membrane systems and native-like crowded milieus. Addition of crowding agents such as Ficoll and its monomeric unit, sucrose, gradually favors clustering of Ras proteins in forming small oligomers in the bulk; only at very high crowder concentrations association is disfavored.

scholarly journals Structural Effects of Cation Binding to DPPC Monolayers

2020 ◽  
Author(s):  
Matti Javanainen ◽  
Wei Hua ◽  
Ondrej Tichacek ◽  
Pauline Delcroix ◽  
Lukasz Cwiklik ◽  
...  
Keyword(s):  
Radical Change ◽  
Binding Mode ◽  
Cation Binding ◽  
Head Group ◽  
Binding Modes ◽  
Sum Frequency ◽  
Area Per Lipid ◽  
Simulation And Experiment ◽  
Lipid Head Group ◽  
Dynamics Simulations

Ions at the two sides of the plasma membrane maintain the transmembrane potential, participate in signaling, and affect the properties of the membrane itself. The extracellular leaflet is particularly enriched in phosphatidylcholine lipids an under the influence of Na+, Ca2+, and Cl− ions. In this work, we combined molecular dynamics simulations performed using state-of-the-art models with vibrational sum frequency generation (VSFG) spectroscopy to study the effects of these key ions on the structure of dipalmitoylphosphatidylcholine. We used lipid monolayers as a proxy for membranes, as this approach enabled a direct comparison between simulation and experiment. We find that the effects of Na+ are minor. Ca2+, on the other hand, strongly affects the lipid head group conformations and induces a tighter packing of lipids, thus promoting the liquid condensed phase. It does so by binding to both the phosphate and carbonyl oxygens via direct and water-mediated binding modes, the ratios of which depend on the monolayer packing. Clustering analysis performed on simulation data revealed that changes in area per lipid or CaCl2 concentration both affect the head group conformations, yet their effects are anti-correlated. Cations at the monolayer surface also attract Cl−, which at large CaCl2 concentrations penetrates deep to the monolayer. This phenomenon coincides with a radical change in the VSFG spectra of the phosphate group, thus indicating the emergence of a new binding mode.

scholarly journals Docosahexaenoic Acid and Eicosapentaenoic Acid Induce Changes in the Physical Properties of a Lipid Bilayer Model Membrane

2006 ◽  
Vol 54 (1) ◽  
pp. 68-71 ◽  
Author(s):  
Yoshinori Onuki ◽  
Mariko Morishita ◽  
Yoshiyuki Chiba ◽  
Shinji Tokiwa ◽  
Kozo Takayama
Keyword(s):  
Docosahexaenoic Acid ◽  
Eicosapentaenoic Acid ◽  
Physical Properties ◽  
Lipid Bilayer ◽  
Model Membrane

scholarly journals Specific Radius Change of Quantum Dot inside the Lipid Bilayer by Charge Effect of Lipid Head-Group

2018 ◽  
Vol 08 (03) ◽  
pp. 163-175
Author(s):  
Soon Ki Sung ◽  
Hyuk Kyu Pak ◽  
Jong Hyeok Kwak ◽  
Sang Weon Lee ◽  
Young Ha Kim ◽  
...  
Keyword(s):  
Quantum Dot ◽  
Lipid Bilayer ◽  
Head Group ◽  
Charge Effect ◽  
Lipid Head Group

scholarly journals Influenza A M2 Spans the Membrane Bilayer, Perturbs its Organization and Differentiates the Effect of Amantadine and Spiro[pyrrolidine-2,2'-adamantane] AK13 on Lipids

2019 ◽  
Author(s):  
Athina Konstantinidi ◽  
Maria Chountoulesi ◽  
Nikolaos Naziris ◽  
Barbara Sartori ◽  
Heinz Amenitsch ◽  
...  
Keyword(s):  
Influenza A ◽  
Acyl Chain ◽  
Md Simulations ◽  
Head Group ◽  
Ammonium Group ◽  
Drug Molecules ◽  
Carboxylate Groups ◽  
Head Surface ◽  
Lipid Head Group ◽  
Phosphate Groups

The investigation and observations made for the M2TM, excess aminoadamantane ligands in DMPC were made using the simpler version of biophysical methods including SDC, SAXS and WAXS, MD simulations and ssNMR. 1H, 31P ssNMR and MD simulations, showed that M2TM in apo form or drug-bound form span the membrane interacting strongly with lipid acyl chain tails and the phosphate groups of the polar head surface. The MD simulations showed that the drugs anchor through their ammonium group with the lipid phosphate and occasionally with M2TM asparagine-44 carboxylate groups. The 13C ssNMR experiments allow the inspection of excess drug molecules and the assessment of its impact on the lipid head-group region. At low peptide concentrations of influenza A M2TM tetramer in DPMC bilayer, two lipid domains were observed that likely correspond to the M2TM boundary lipids and the bulk-like lipids. At high peptide concentrations, one domain was identified which constitute essentially all of the lipids which behave as boundary. This effect is likely due, according to the MD simulations, to the preference of AK13 to locate in closer vicinity to M2TM compared to Amt as well as the stronger ionic interactions of Amt primary ammonium group with phosphate groups, compared with the secondary buried ammonium group in AK13.<br>

Spotting Differences in Molecular Dynamic Simulations of Influenza A M2 Protein-Ligand Complexes by Varying M2 construct, Lipid Bilayer and Force Field

2019 ◽  
Author(s):  
Dimitrios Kolokouris ◽  
Iris Kalenderoglou ◽  
Panagiotis Lagarias ◽  
Antonios Kolocouris
Keyword(s):  
Molecular Dynamic ◽  
Lipid Bilayer ◽  
Influenza A ◽  
Md Simulations ◽  
Membrane Curvature ◽  
Buffer Size ◽  
M2 Protein ◽  
Dynamic Simulations ◽  
Amphipathic Helices ◽  
Drug Protein Binding

<p>We studied by molecular dynamic (MD) simulations systems including the inward<sub>closed</sub> state of influenza A M2 protein in complex with aminoadamantane drugs in membrane bilayers. We varied the M2 construct and performed MD simulations in M2TM or M2TM with amphipathic helices (M2AH). We also varied the lipid bilayer by changing either the lipid, DMPC or POPC, POPE or POPC/cholesterol (chol), or the lipids buffer size, 10x10 Å<sup>2 </sup>or 20x20 Å<sup>2</sup>. We aimed to suggest optimal system conditions for the computational description of this ion channel and related systems. Measures performed include quantities that are available experimentally and include: (a) the position of ligand, waters and chlorine anion inside the M2 pore, (b) the passage of waters from the outward Val27 gate of M2 S31N in complex with an aminoadamantane-aryl head blocker, (c) M2 orientation, (d) the AHs conformation and structure which is affected from interactions with lipids and chol and is important for membrane curvature and virus budding. In several cases we tested OPLS2005, which is routinely applied to describe drug-protein binding, and CHARMM36 which describes reliably protein conformation. We found that for the description of the ligands position inside the M2 pore, a 10x10 Å<sup>2</sup> lipids buffer in DMPC is needed when M2TM is used but 20x20 Å<sup>2</sup> lipids buffer of the softer POPC; when M2AH is used all 10x10 Å<sup>2</sup> lipid buffers with any of the tested lipids can be used. For the passage of waters at least M2AH with a 10x10 Å<sup>2</sup> lipid buffer is needed. The folding conformation of AHs which is defined from hydrogen bonding interactions with the bilayer and the complex with chol is described well with a 10x10 Å<sup>2</sup> lipids buffer and CHARMM36. </p>

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