Scattering Density Profile Model of POPG Bilayers As Determined by Molecular Dynamics Simulations and Small-Angle Neutron and X-ray Scattering Experiments

Kučerka, Norbert; Holland, Bryan W.; Gray, C.G.; Tomberli, Bruno; Katsaras, John

doi:10.1021/jp208920h

Cited by 93 publications

(103 citation statements)

References 37 publications

(96 reference statements)

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“…For a typical GUV with a diameter of 40 μm, the number of lipid molecules that the GUV contains is ~1.5 × 10 10 (lipid area ~0.65 nm 2 for POPC and POPG [59, 60]). When the GUV is submerged in 200 μL of 5 μM peptide solution, the estimated peptide to lipid ratio (P/L) is 4.0 × 10 4 .…”

Section: Discussionmentioning

confidence: 99%

Modulation of lipid membrane structural and mechanical properties by a peptidomimetic derived from reduced amide scaffold

Khadka¹,

Teng²,

Cai³

et al. 2017

Biochimica et Biophysica Acta (BBA) - Biomembranes

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Understanding how antimicrobial peptidomimetics interact with lipid membranes is important in battling multidrug resistant bacterial pathogens. We study the effects of a recently reported peptidomimetic on lipid bilayer structural and mechanical properties. The compound referred to as E107-3 is synthesized based on the acylated reduced amide scaffold and has been shown to exhibit good antimicrobial potency. Our vesicle leakage essay indicates that the compound increases lipid bilayer permeability. We use micropipette aspiration to explore the kinetic response of giant unilamellar vesicles (GUVs). Exposure to the compound causes the GUV protrusion length LP to spontaneously increase and then decrease, followed by GUV rupture. Solution atomic force microscopy (AFM) is used to visualize lipid bilayer structural modulation within a nanoscopic regime. Unlike melittin, which produces pore-like structures, the peptidomimetic compound is found to induce nanoscopic heterogeneous structures. Finally, we use AFM-based force spectroscopy to study the impact of the compound on lipid bilayer mechanical properties. We find that incremental addition of the compound to planar lipid bilayers results in a moderate decrease of the bilayer puncture force FP and a 39% decrease of the bilayer area compressibility modulus KA. To explain our experimental data, we propose a membrane interaction model encompassing disruption of lipid chain packing and extraction of lipid molecules. The later action mode is supported by our observation of a double-bilayer structure in the presence of fusogenic calcium ions.

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Section: Discussionmentioning

confidence: 99%

Modulation of lipid membrane structural and mechanical properties by a peptidomimetic derived from reduced amide scaffold

Khadka¹,

Teng²,

Cai³

et al. 2017

Biochimica et Biophysica Acta (BBA) - Biomembranes

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“…Data analysis is carried out using a single structural model which underlies all of the various scattering density profiles, or the so-called SDP model. The original model developed for PC 20 lipids has been extended recently for PG, 67 PS, 36 and ether 33 lipids. We continue this development by extending the SDP model to PE bilayers.…”

Section: ■ Materials and Methodsmentioning

confidence: 99%

Molecular Structures of Fluid Phosphatidylethanolamine Bilayers Obtained from Simulation-to-Experiment Comparisons and Experimental Scattering Density Profiles

et al. 2014

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Vous avez des questions? Nous pouvons vous aider. Pour communiquer directement avec un auteur, consultez la première page de la revue dans laquelle son article a été publié afin de trouver ses coordonnées. Si vous n'arrivez pas à les repérer, communiquez avec nous à PublicationsArchive-ArchivesPublications@nrc-cnrc.gc.ca. Questions? Contact the NRC Publications Archive team atPublicationsArchive-ArchivesPublications@nrc-cnrc.gc.ca. If you wish to email the authors directly, please see the first page of the publication for their contact information. NRC Publications Archive Archives des publications du CNRCThis publication could be one of several versions: author's original, accepted manuscript or the publisher's version. / La version de cette publication peut être l'une des suivantes : la version prépublication de l'auteur, la version acceptée du manuscrit ou la version de l'éditeur. For the publisher's version, please access the DOI link below./ Pour consulter la version de l'éditeur, utilisez le lien DOI ci-dessous.http://doi.org/10.1021/jp511159qAccess and use of this website and the material on it are subject to the Terms and Conditions set forth at NRC Publications Record / Notice d'Archives des publications de CNRC:http://nparc.cisti-icist.nrc-cnrc.gc.ca/eng/view/object/?id=9f16af25-9d91-47f7-b19b-387fe4c4022b http://nparc.cisti-icist.nrc-cnrc.gc.ca/fra/voir/objet/?id=9f16af25-9d91-47f7-b19b-387fe4c4022b ABSTRACT: Following our previous efforts in determining the structures of commonly used PC, PG, and PS bilayers, we continue our studies of fully hydrated, fluid phase PE bilayers. The newly designed parsing scheme for PE bilayers was based on extensive MD simulations, and is utilized in the SDP analysis of both X-ray and neutron (contrast varied) scattering measurements. Obtained experimental scattering form factors are directly compared to our simulation results, and can serve as a benchmark for future developed force fields. Among the evaluated structural parameters, namely, area per lipid A, overall bilayer thickness D B , and hydrocarbon region thickness 2D C , the PE bilayer response to changing temperature is similar to previously studied bilayers with different headgroups. On the other hand, the reduced hydration of PE headgroups, as well as the strong hydrogen bonding between PE headgroups, dramatically affects lateral packing within the bilayer. Despite sharing the same glycerol backbone, a markedly smaller area per lipid distinguishes PE from other bilayers (i.e., PC, PG, and PS) studied to date. Overall, our data are consistent with the notion that lipid headgroups govern bilayer packing, while hydrocarbon chains dominate the bilayer's response to temperature changes. ■ INTRODUCTIONMembranes that surround cells and separate their contents from the external environment are ubiquitous in nature. Biological membranes consist mainly of lipids and proteins, where it is widely accepted that the membrane's underlying structure is imparted by the lipid bilayer. As such, tremendous effort has been expe...

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“…SLDs for the lipids were calculated from atomic composition, c i , with coherent scattering lengths, b c , and molecular volumes, V m , from molecular dynamics simulations 74,75 according to To the best of our knowledge, there are no available data from measurements or simulations on the headgroup volume of CL, and we therefore used the molecular density of PG 76,77 because CL structurally consists of two linked PG molecules. The calculated lipid SLD values were allowed to vary up to 10% during modeling.…”

Section: −71mentioning

confidence: 99%

Adsorption of α-Synuclein to Supported Lipid Bilayers: Positioning and Role of Electrostatics

Hellstrand

Grey

Ainalem

et al. 2013

ACS Chem. Neurosci.

102

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An amyloid form of the protein α-synuclein is the major component of the intraneuronal inclusions called Lewy bodies, which are the neuropathological hallmark of Parkinson's disease (PD). α-Synuclein is known to associate with anionic lipid membranes, and interactions between aggregating α-synuclein and cellular membranes are thought to be important for PD pathology. We have studied the molecular determinants for adsorption of monomeric α-synuclein to planar model lipid membranes composed of zwitterionic phosphatidylcholine alone or in a mixture with anionic phosphatidylserine (relevant for plasma membranes) or anionic cardiolipin (relevant for mitochondrial membranes). We studied the adsorption of the protein to supported bilayers, the position of the protein within and outside the bilayer, and structural changes in the model membranes using two complementary techniquesquartz crystal microbalance with dissipation monitoring, and neutron reflectometry. We found that the interaction and adsorbed conformation depend on membrane charge, protein charge, and electrostatic screening. The results imply that α-synuclein adsorbs in the headgroup region of anionic lipid bilayers with extensions into the bulk but does not penetrate deeply into or across the hydrophobic acyl chain region. The adsorption to anionic bilayers leads to a small perturbation of the acyl chain packing that is independent of anionic headgroup identity. We also explored the effect of changing the area per headgroup in the lipid bilayer by comparing model systems with different degrees of acyl chain saturation. An increase in area per lipid headgroup leads to an increase in the level of α-synuclein adsorption with a reduced water content in the acyl chain layer. In conclusion, the association of α-synuclein to membranes and its adsorbed conformation are of electrostatic origin, combined with van der Waals interactions, but with a very weak correlation to the molecular structure of the anionic lipid headgroup. The perturbation of the acyl chain packing upon monomeric protein adsorption favors association with unsaturated phospholipids preferentially found in the neuronal membrane.

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Scattering Density Profile Model of POPG Bilayers As Determined by Molecular Dynamics Simulations and Small-Angle Neutron and X-ray Scattering Experiments

Cited by 93 publications

References 37 publications

Modulation of lipid membrane structural and mechanical properties by a peptidomimetic derived from reduced amide scaffold

Modulation of lipid membrane structural and mechanical properties by a peptidomimetic derived from reduced amide scaffold

Molecular Structures of Fluid Phosphatidylethanolamine Bilayers Obtained from Simulation-to-Experiment Comparisons and Experimental Scattering Density Profiles

Adsorption of α-Synuclein to Supported Lipid Bilayers: Positioning and Role of Electrostatics

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