scholarly journals Lipid flip-flop and desorption from supported lipid bilayers is independent of curvature

PLoS ONE ◽  
2020 ◽  
Vol 15 (12) ◽  
pp. e0244460
Author(s):  
Haoyuan Jing ◽  
Yanbin Wang ◽  
Parth Rakesh Desai ◽  
Kumaran S. Ramamurthi ◽  
Siddhartha Das
Keyword(s):  
Lipid Bilayer ◽  
Lipid Bilayers ◽  
Md Simulations ◽  
Packing Fraction ◽  
Membrane Curvature ◽  
Supported Lipid Bilayer ◽  
Flip Flop ◽  
Lipid Molecule ◽  
Membrane Asymmetry ◽  
Cell Shapes

Flip-flop of lipids of the lipid bilayer (LBL) constituting the plasma membrane (PM) plays a crucial role in a myriad of events ranging from cellular signaling and regulation of cell shapes to cell homeostasis, membrane asymmetry, phagocytosis, and cell apoptosis. While extensive research has been conducted to probe the lipid flip flop of planar lipid bilayers (LBLs), less is known regarding lipid flip-flop for highly curved, nanoscopic LBL systems despite the vast importance of membrane curvature in defining the morphology of cells and organelles and in maintaining a variety of cellular functions, enabling trafficking, and recruiting and localizing shape-responsive proteins. In this paper, we conduct molecular dynamics (MD) simulations to study the energetics, structure, and configuration of a lipid molecule undergoing flip-flop and desorption in a highly curved LBL, represented as a nanoparticle-supported lipid bilayer (NPSLBL) system. We compare our findings against those of a planar substrate supported lipid bilayer (PSSLBL). Our MD simulation results reveal that despite the vast differences in the curvature and other curvature-dictated properties (e.g., lipid packing fraction, difference in the number of lipids between inner and outer leaflets, etc.) between the NPSLBL and the PSSLBL, the energetics of lipid flip-flop and lipid desorption as well as the configuration of the lipid molecule undergoing lipid flip-flop are very similar for the NPSLBL and the PSSLBL. In other words, our results establish that the curvature of the LBL plays an insignificant role in lipid flip-flop and desorption.

scholarly journals Does alpha-tocopherol flip-flop help to protect membranes against oxidation?

2018 ◽  
Author(s):  
Phansiri Boonnoy ◽  
Mikko Karttunen ◽  
Jirasak Wong-ekkabut
Keyword(s):  
Free Energy ◽  
Free Radicals ◽  
Lipid Bilayer ◽  
Lipid Bilayers ◽  
Md Simulations ◽  
Free Energy Calculations ◽  
Alpha Tocopherol ◽  
Oxidized Lipids ◽  
Hydroxyl Groups ◽  
Flip Flop

AbstractAlpha-tocopherols (α-toc) are crucial in protecting biological membranes against oxidation by free radicals. We investigate the behavior of α-toc molecules in lipid bilayers containing oxidized lipids by molecular dynamics (MD) simulations. To verify the approach, the location and orientation of α-toc are first shown to be in agreement with previous experimental results. The simulations further show that α-toc molecules stay inside the lipid bilayer with their hydroxyl groups in contact with the bilayer surface. Interestingly, interbilayer α-toc flip-flop was observed in both oxidized and non-oxidized bilayers with significantly higher frequency in aldehyde lipid bilayer. Free energy calculations were performed and estimates of the flip-flop rates across the bilayers were determined. As the main finding, our results show that the presence of oxidized lipids leads to a significant decrease of free energy barriers and that the flip-flop rates depend on the type of oxidized lipid present. Our results suggest that α-toc molecules could potentially act as high efficacy scavengers of free radicals to protect membranes from oxidative attack and help stabilize them under oxidative stress.

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>

scholarly journals Theoretical and computational modeling of peptide-lipid bilayer interaction studied by dynamic force spectroscopy

2019 ◽  
Author(s):  
◽  
Milica Utjesanovic
Keyword(s):  
Computational Modeling ◽  
Lipid Bilayer ◽  
Lipid Bilayers ◽  
Lipid Membranes ◽  
Lipid Membrane ◽  
Conformational Dynamics ◽  
Quantitative Description ◽  
Md Simulations ◽  
Dynamic Force ◽  
Detachment Rate

This thesis consists of three interrelated theoretical and computational modeling projects that investigate different aspects of peptide-lipid membrane interactions. (1) A general theoretical approach is formulated for the quantitative description of the detachment force distribution, P(F), and the corresponding force dependent detachment rate, k(F), of a peptide from a lipid bilayer, by assuming that peptide detachment from lipid membranes occurs stochastically along a few dominant diffusive pathways. Besides providing a consistent interpretation of the experimental data, the new method also predicts that k(F) exhibits catch-bond behavior (when, counter intuitively, the detachment rate decreases with increasing force). (2) The proposed multiple detachment pathways method is tested and validated for a particular peptide (SecA2-11) interacting with both zwitterionic POPC lipid and polar E. Coli membranes. Furthermore, molecular dynamics (MD) simulations are used to explored the conformational dynamics of SecA2-11 during its interaction with both POPC and anionic POPG lipid bilayers. (3) Finally, MD simulations are used to explore the conformational dynamics and energetics of the peptide melittin (MWT) and its diastereomer (MD4) interacting with POPC and POPG lipid bilayers. The obtained results provide further insight into the role of secondary structure in peptide-lipid bilayer interactions.

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>

Kinetic evolution of DOPC lipid bilayers exposed to α-cyclodextrins

Soft Matter ◽  
2018 ◽  
Vol 14 (28) ◽  
pp. 5800-5810 ◽  
Author(s):  
Monika Kluzek ◽  
Marc Schmutz ◽  
Carlos M. Marques ◽  
Fabrice Thalmann
Keyword(s):  
Lipid Bilayer ◽  
Lipid Bilayers ◽  
Confocal Laser Scanning Microscopy ◽  
Laser Scanning ◽  
Laser Scanning Microscopy ◽  
Confocal Laser Scanning ◽  
Scanning Microscopy ◽  
Confocal Laser ◽  
Supported Lipid Bilayer ◽  
Microscopy Image

Confocal laser scanning microscopy image of a fluorescent supported lipid bilayer exposed to a 15 mM solution of α-cyclodextrin.

Transport and Organization of Cholesterol in a Planar Solid-Supported Lipid Bilayer Depend on the Phospholipid Flip-Flop Rate

Langmuir ◽  
2016 ◽  
Vol 32 (44) ◽  
pp. 11681-11689 ◽  
Author(s):  
Ting Yu ◽  
Guangnan Zhou ◽  
Xia Hu ◽  
Shuji Ye
Keyword(s):  
Lipid Bilayer ◽  
Supported Lipid Bilayer ◽  
Flip Flop

Supported lipid bilayer repair mediated by AH peptide

2016 ◽  
Vol 18 (4) ◽  
pp. 3040-3047 ◽  
Author(s):  
Min Chul Kim ◽  
Anders Gunnarsson ◽  
Seyed R. Tabaei ◽  
Fredrik Höök ◽  
Nam-Joon Cho
Keyword(s):  
Lipid Bilayer ◽  
Lipid Bilayers ◽  
Silicon Oxide ◽  
Supported Lipid Bilayers ◽  
High Quality ◽  
Supported Lipid Bilayer

High quality and complete supported lipid bilayers are formed on silicon oxide by employing an AH peptide mediated repair step.

scholarly journals Single Lipid Molecule Dynamics on Supported Lipid Bilayers with Membrane Curvature

Membranes ◽  
2017 ◽  
Vol 7 (1) ◽  
pp. 15 ◽  
Author(s):  
Philip Cheney ◽  
Alan Weisgerber ◽  
Alec Feuerbach ◽  
Michelle Knowles
Keyword(s):  
Lipid Bilayers ◽  
Membrane Curvature ◽  
Supported Lipid Bilayers ◽  
Lipid Molecule ◽  
Molecule Dynamics

scholarly journals Molecular Basis of Mechanotransduction in Living Cells

2001 ◽  
Vol 81 (2) ◽  
pp. 685-740 ◽  
Author(s):  
Owen P. Hamill ◽  
Boris Martinac
Keyword(s):  
Lipid Bilayer ◽  
Lipid Bilayers ◽  
Animal Cell ◽  
Membrane Curvature ◽  
Energetic Cost ◽  
Water Volume ◽  
Elastic Membrane ◽  
Animal Cells ◽  
Hydrophobic Mismatch ◽  
Membrane Area

The simplest cell-like structure, the lipid bilayer vesicle, can respond to mechanical deformation by elastic membrane dilation/thinning and curvature changes. When a protein is inserted in the lipid bilayer, an energetic cost may arise because of hydrophobic mismatch between the protein and bilayer. Localized changes in bilayer thickness and curvature may compensate for this mismatch. The peptides alamethicin and gramicidin and the bacterial membrane protein MscL form mechanically gated (MG) channels when inserted in lipid bilayers. Their mechanosensitivity may arise because channel opening is associated with a change in the protein's membrane-occupied area, its hydrophobic mismatch with the bilayer, excluded water volume, or a combination of these effects. As a consequence, bilayer dilation/thinning or changes in local membrane curvature may shift the equilibrium between channel conformations. Recent evidence indicates that MG channels in specific animal cell types (e.g., Xenopus oocytes) are also gated directly by bilayer tension. However, animal cells lack the rigid cell wall that protects bacteria and plants cells from excessive expansion of their bilayer. Instead, a cortical cytoskeleton (CSK) provides a structural framework that allows the animal cell to maintain a stable excess membrane area (i.e., for its volume occupied by a sphere) in the form of membrane folds, ruffles, and microvilli. This excess membrane provides an immediate membrane reserve that may protect the bilayer from sudden changes in bilayer tension. Contractile elements within the CSK may locally slacken or tighten bilayer tension to regulate mechanosensitivity, whereas membrane blebbing and tight seal patch formation, by using up membrane reserves, may increase membrane mechanosensitivity. In specific cases, extracellular and/or CSK proteins (i.e., tethers) may transmit mechanical forces to the process (e.g., hair cell MG channels, MS intracellular Ca2+release, and transmitter release) without increasing tension in the lipid bilayer.

scholarly journals Membrane attack complex formation on a supported lipid bilayer: initial steps towards a CARPA predictor nanodevice

2015 ◽  
Vol 7 (3) ◽  
Author(s):  
Saziye Yorulmaz ◽  
Seyed R. Tabaei ◽  
Myunghee Kim ◽  
Jeongeun Seo ◽  
Walter Hunziker ◽  
...  
Keyword(s):  
Real Time ◽  
Lipid Bilayer ◽  
Lipid Bilayers ◽  
Ambient Medium ◽  
Membrane Attack Complex ◽  
Common Adverse Effect ◽  
Individual Risk ◽  
Supported Lipid Bilayer ◽  
Activation Assay

AbstractThe rapid advance of nanomedicines and biologicals in pharmacotherapy gives increasing importance to a common adverse effect of these modern therapeutics: complement (C) activation-related pseudoallergy (CARPA). CARPA is a relatively frequent and potentially lethal acute immune toxicity of many intravenous drugs that contain nanoparticles or proteins, whose prediction by laboratory or in vivo testing has not yet been solved. Preliminary studies suggest that proneness of the drug to cause C activation in the blood of patients may predict the individual risk of CARPA, thus, a sensitive and rapid bedside assay for individualized assessment of a drug’s C activating potential could alleviate the CARPA problem. The goal of the present study was to lay down the foundations of a novel approach for real-time sensing of C activation on a supported lipid bilayer platform. We utilized the quartz crystal microbalance with dissipation (QCM-D) monitoring technique to measure the self-assembly of C terminal complex (or membrane attack complex [MAC]) on supported lipid bilayers rapidly assembled by the solvent-assisted lipid bilayer (SALB) formation method, as an immediate measure of C activation. By measuring the changes in frequency and energy dissipation of deposited protein, the technique allows extremely sensitive real-time quantification of the sequential assembly of MAC from its molecular components (C5b-6, C7, C8 and C9) and hence, measure C activation in the ambient medium. The present paper delineates the technique and our initial evidence with purified C proteins that the approach enables sensitive and rapid (real-time) quantification of MAC formation on a silicon-supported planar (phospho) lipid bilayer, which can be used as an endpoint in a clinically useful bedside C activation assay.

Sign in / Sign up

Export Citation Format

Share Document