Polyunsaturated phospholipids facilitate membrane deformation and fission by endocytic proteins

Science ◽  
2014 ◽  
Vol 345 (6197) ◽  
pp. 693-697 ◽  
Author(s):  
Mathieu Pinot ◽  
Stefano Vanni ◽  
Sophie Pagnotta ◽  
Sandra Lacas-Gervais ◽  
Laurie-Anne Payet ◽  
...  
Keyword(s):  
Membrane Curvature ◽  
Membrane Properties ◽  
Energetic Cost ◽  
Synthetic Membranes ◽  
Acyl Chains ◽  
Biochemical Measurements ◽  
Membrane Bending ◽  
Pulling Force ◽  
Dynamics Simulations ◽  
Cellular Organelles

Phospholipids (PLs) with polyunsaturated acyl chains are extremely abundant in a few specialized cellular organelles such as synaptic vesicles and photoreceptor discs, but their effect on membrane properties is poorly understood. Here, we found that polyunsaturated PLs increased the ability of dynamin and endophilin to deform and vesiculate synthetic membranes. When cells incorporated polyunsaturated fatty acids into PLs, the plasma membrane became more amenable to deformation by a pulling force and the rate of endocytosis was accelerated, in particular, under conditions in which cholesterol was limiting. Molecular dynamics simulations and biochemical measurements indicated that polyunsaturated PLs adapted their conformation to membrane curvature. Thus, by reducing the energetic cost of membrane bending and fission, polyunsaturated PLs may help to support rapid endocytosis.

scholarly journals Roughness of a transmembrane peptide reduces lipid membrane dynamics

2016 ◽  
Author(s):  
Marie Olšinová ◽  
Piotr Jurkiewicz ◽  
Jan Sýkora ◽  
Ján Sabó ◽  
Martin Hof ◽  
...  
Keyword(s):  
Rough Surface ◽  
Lipid Membrane ◽  
Cholesterol Content ◽  
Membrane Dynamics ◽  
Membrane Properties ◽  
Helical Structures ◽  
Transmembrane Peptides ◽  
Acyl Chains ◽  
Dynamics Simulations ◽  
And Function

Transmembrane domains integrate proteins into cellular membranes and support their function. The capacity of these prevalently a-helical structures in mammals to influence membrane properties is poorly understood. Combining experiments with molecular dynamics simulations, we provide evidence that helical transmembrane peptides with their rough surface reduce lateral mobility of membrane constituents. The molecular mechanism involves trapping of lipid acyl chains on the rough surface and segregation of cholesterol from the vicinity of peptides. The observations are supported by our toy model indicating strong effect of rough objects on membrane dynamics. Herein described effect has implications for the organization and function of biological membranes, especially the plasma membrane with high cholesterol content.

scholarly journals Clustering and dynamics of crowded proteins near membranes and their influence on membrane bending

2019 ◽  
Vol 116 (49) ◽  
pp. 24562-24567 ◽  
Author(s):  
Grzegorz Nawrocki ◽  
Wonpil Im ◽  
Yuji Sugita ◽  
Michael Feig
Keyword(s):  
Membrane Surface ◽  
Membrane Curvature ◽  
Phospholipid Bilayer ◽  
Protein Solutions ◽  
Protein Diffusion ◽  
Depletion Zone ◽  
Head Groups ◽  
Membrane Contacts ◽  
Membrane Bending ◽  
Dynamics Simulations

Atomistic molecular dynamics simulations of concentrated protein solutions in the presence of a phospholipid bilayer are presented to gain insights into the dynamics and interactions at the cytosol–membrane interface. The main finding is that proteins that are not known to specifically interact with membranes are preferentially excluded from the membrane, leaving a depletion zone near the membrane surface. As a consequence, effective protein concentrations increase, leading to increased protein contacts and clustering, whereas protein diffusion becomes faster near the membrane for proteins that do occasionally enter the depletion zone. Since protein–membrane contacts are infrequent and short-lived in this study, the structure of the lipid bilayer remains largely unaffected by the crowded protein solution, but when proteins do contact lipid head groups, small but statistically significant local membrane curvature is induced, on average.

scholarly journals Curvature increases permeability of the plasma membrane for ions, water and the anti-cancer drugs cisplatin and gemcitabine

2019 ◽  
Author(s):  
Semen Yesylevskyy ◽  
Timothée Rivel ◽  
Christophe Ramseyer
Keyword(s):  
Molecular Dynamics ◽  
Plasma Membrane ◽  
Molecular Dynamics Simulations ◽  
Membrane Curvature ◽  
Cancer Drugs ◽  
Anti Cancer ◽  
Membrane Bending ◽  
Dynamics Simulations

ABSTRACTIn this work the permeability of a model asymmetric plasma membrane, for ions, water and the anti-cancer drugs cisplatin and gemcitabine is studied by means of all-atom molecular dynamics simulations. It is shown that permeability of the membranes increases from one to three orders of magnitude upon membrane bending depending on the compound and the sign of curvature. Our results show that the membrane curvature is an important factor which should be considered during evaluation of drug translocation.TOC GRAPHICS

scholarly journals Curvature increases permeability of the plasma membrane for ions, water and the anti-cancer drugs cisplatin and gemcitabine

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Semen Yesylevskyy ◽  
Timothée Rivel ◽  
Christophe Ramseyer
Keyword(s):  
Molecular Dynamics ◽  
Plasma Membrane ◽  
Molecular Dynamics Simulations ◽  
Membrane Curvature ◽  
Cancer Drugs ◽  
Anti Cancer ◽  
Membrane Bending ◽  
Dynamics Simulations ◽  
Curved Membrane ◽  
First Time

AbstractIn this work the permeability of a model asymmetric plasma membrane, for ions, water and the anti-cancer drugs cisplatin and gemcitabine is studied by means of all-atom molecular dynamics simulations. It is shown for the first time that permeability of the highly curved membrane increases from one to three orders of magnitude upon membrane bending depending on the compound and the sign of curvature. Our results suggest that the membrane curvature could be an important factor of drug translocation through the membrane.

scholarly journals Diethylstilbestrol Modifies the Structure of Model Membranes and Is Localized Close to the First Carbons of the Fatty Acyl Chains

Biomolecules ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 220
Author(s):  
Alessio Ausili ◽  
Inés Rodríguez-González ◽  
Alejandro Torrecillas ◽  
José A. Teruel ◽  
Juan C. Gómez-Fernández
Keyword(s):  
Membrane Surface ◽  
Water Layer ◽  
Fatty Acyl ◽  
31P Nmr Spectroscopy ◽  
Relaxation Rates ◽  
X Ray Diffraction ◽  
Scanning Calorimetry ◽  
X Ray ◽  
Acyl Chains ◽  
Dynamics Simulations

The synthetic estrogen diethylstilbestrol (DES) is used to treat metastatic carcinomas and prostate cancer. We studied its interaction with membranes and its localization to understand its mechanism of action and side-effects. We used differential scanning calorimetry (DSC) showing that DES fluidized the membrane and has poor solubility in DMPC (1,2-dimyristoyl-sn-glycero-3-phosphocholine) in the fluid state. Using small-angle X-ray diffraction (SAXD), it was observed that DES increased the thickness of the water layer between phospholipid membranes, indicating effects on the membrane surface. DSC, X-ray diffraction, and 31P-NMR spectroscopy were used to study the effect of DES on the Lα-to-HII phase transition, and it was observed that negative curvature of the membrane is promoted by DES, and this effect may be significant to understand its action on membrane enzymes. Using the 1H-NOESY-NMR-MAS technique, cross-relaxation rates for different protons of DES with POPC (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine) protons were calculated, suggesting that the most likely location of DES in the membrane is with the main axis parallel to the surface and close to the first carbons of the fatty acyl chains of POPC. Molecular dynamics simulations were in close agreements with the experimental results regarding the location of DES in phospholipids bilayers.

scholarly journals Membrane potential and dynamics in a ternary lipid mixture: insights from molecular dynamics simulations

2018 ◽  
Vol 20 (23) ◽  
pp. 15841-15851 ◽  
Author(s):  
Xubo Lin ◽  
Vinay Nair ◽  
Yong Zhou ◽  
Alemayehu A. Gorfe
Keyword(s):  
Molecular Dynamics ◽  
Membrane Potential ◽  
Molecular Dynamics Simulations ◽  
Transmembrane Potential ◽  
Lipid Mixture ◽  
Structure And Dynamics ◽  
Head Groups ◽  
Acyl Chains ◽  
Dynamics Simulations

Transmembrane potential modulates the structure and dynamics of lipid head-groups and acyl chains.

Chlorpromazine modulates the morphological macro- and microstructure of endothelial cells

2000 ◽  
Vol 278 (5) ◽  
pp. C873-C878 ◽  
Author(s):  
I. S. Hueck ◽  
H. G. Hollweg ◽  
G. W. Schmid-Schönbein ◽  
G. M. Artmann
Keyword(s):  
Endothelial Cells ◽  
Antipsychotic Agent ◽  
Membrane Curvature ◽  
Phospholipid Bilayer ◽  
Aortic Endothelial Cells ◽  
Bovine Aortic Endothelial Cells ◽  
Cellular Attachment ◽  
Transmission Electron ◽  
Membrane Adhesion ◽  
Membrane Bending

Chlorpromazine (CP), an amphipathic, antipsychotic agent, causes concave membrane bending in red blood cells with formation of stomatocytic shapes by modulation of the phospholipid bilayer. This study was designed to investigate the effects of CP on the shape of bovine aortic endothelial cells (BAEC) and their membranes in confluent monolayers with phase-contrast and transmission electron microscopy. Exposure of BAECs to nanomolar levels of CP leads to membrane curvature changes. With increasing CP concentrations, the membrane assumed a shape with enhanced numbers of intracellular caveolae and projection of pseudopodia at all junctions. At higher CP concentrations (up to 150 μM), the endothelial cells assumed almost spherical shapes. The evidence suggests that CP may affect lipid bilayer bending of BAECs in analogy with previous observations on erythrocytes, supporting the formation of caveolae and pseudopodia in BAECs due to the induction of concave membrane bending, as well as an effect on endothelial cell membrane adhesion at higher CP concentrations with loss of cellular attachment at junctions.

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

2015 ◽  
Vol 17 (35) ◽  
pp. 22736-22748 ◽  
Author(s):  
João R. Robalo ◽  
J. P. Prates Ramalho ◽  
Daniel Huster ◽  
Luís M. S. Loura
Keyword(s):  
Molecular Dynamics ◽  
Membrane Properties ◽  
Side Chain ◽  
Side Chains ◽  
Aliphatic Side Chain ◽  
Acyl Chains ◽  
Hydrophobic Matching ◽  
Phospholipid Acyl Chains

Cholesterol provides best hydrophobic matching, induces maximal membrane ordering, and displays highest preference for saturated phospholipid acyl chains, among a homologous ser ies of sterols with side chains of varying lengths.

Membrane Curvature Induced by Sugar and Polymer Solutions

1997 ◽  
Vol 489 ◽  
Author(s):  
H.-G. Döbereiner ◽  
A. Lehmann ◽  
W. Goedel ◽  
O. Selchow ◽  
R. Lipowsky
Keyword(s):  
Polymer Solutions ◽  
Lipid Vesicles ◽  
Membrane Curvature ◽  
Elastic Membrane ◽  
Spontaneous Curvature ◽  
Membrane Asymmetry ◽  
Bending Modulus ◽  
Bending Elasticity ◽  
Cellular Organelles

AbstractWe monitor the effect of transversal membrane asymmetry on the morphology of giant uni-lamellar vesicles in sugar and polymer solutions. The shapes of fluid lipid vesicles are governed by the bending elasticity of their membrane which is characterized by the bending modulus and the spontaneous curvature of the bilayer. We present a recently developed technique for the measurement of the spontaneous curvature using quantitative phase contrast microscopy. Different mechanisms for elastic membrane asymmetry and the role of the bending energy concept for the morphology of cellular organelles are discussed.

scholarly journals Characterization of Lipid Membrane Properties for Tunable Electroporation

2012 ◽  
Author(s):  
H. Jeremy Cho ◽  
Shalabh C. Maroo ◽  
Evelyn N. Wang
Keyword(s):  
Lipid Bilayers ◽  
Lipid Membrane ◽  
Contact Angle Measurement ◽  
Angle Measurement ◽  
Membrane Properties ◽  
Force Microscopy ◽  
Packing Structure ◽  
Atomic Force ◽  
Dynamics Simulations

Lipid bilayers form nanopores on the application of an electric field. This process of electroporation can be utilized in different applications ranging from targeted drug delivery in cells to nano-gating membrane for engineering applications. However, the ease of electroporation is dependent on the surface energy of the lipid layers and thus directly related to the packing structure of the lipid molecules. 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) lipid monolayers were deposited on a mica substrate using the Langmuir-Blodgett (LB) technique at different packing densities and analyzed using atomic force microscopy (AFM). The wetting behavior of these monolayers was investigated by contact angle measurement and molecular dynamics simulations. It was found that an equilibrium packing density of liquid-condensed (LC) phase DPPC likely exists and that water molecules can penetrate the monolayer displacing the lipid molecules. The surface tension of the monolayer in air and water was obtained along with its breakthrough force.

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