scholarly journals Magainin 2 and PGLa in Bacterial Membrane Mimics I: Peptide-Peptide and Lipid-Peptide Interactions

2019 ◽  
Author(s):  
Michael Pachler ◽  
Ivo Kabelka ◽  
Marie-Sousai Appavou ◽  
Karl Lohner ◽  
Robert Vácha ◽  
...  
Keyword(s):  
Antimicrobial Peptides ◽  
Lipid Vesicles ◽  
Coarse Grained ◽  
Joint Analysis ◽  
Synergistic Activity ◽  
Salt Bridges ◽  
Membrane Perturbation ◽  
High Concentrations ◽  
Dynamics Simulations ◽  
The Individual

ABSTRACTWe addressed the onset of synergistic activity of the two well-studied antimicrobial peptides magainin 2 (MG2a) and PGLa using lipid-only mimics of Gram-negative cytoplasmic membranes. Specifically, we coupled a joint analysis of small-angle X-ray and neutron scattering experiments on fully hydrated lipid vesicles in the presence of MG2a and L18W-PGLa to all-atom and coarse-grained molecular dynamics simulations. In agreement with previous studies both peptides, as well as their equimolar mixture, were found to remain in a surface-aligned topology upon membrane insertion and to induce significant membrane perturbation as evidenced by membrane thinning and hydrocarbon order parameter changes in the vicinity of the inserted peptide. These effects were particularly pronounced for the so called synergistic mixture of 1:1 (mol/mol) L18W-PGLa/MG2a and cannot be accounted for by a linear combination of the membrane perturbations of two peptides individually. Our data are consistent with parallel heterodimers forming at much lower concentrations than previously considered, but which do not induce a synergistic leakage of dyes. Our simulations further show that the heterodimers interact via salt bridges and hydrophobic forces, which apparently makes them more stable than putatively formed antiparallel L18W-PGLa and MG2a homodimers. Moreover, dimerization of L18W-PGLa and MG2a leads to a relocation of the peptides within the lipid headgroup regime as compared to the individual peptides. The early onset of dimerization of L18W-PGLa and MG2a at low peptide concentrations consequently appears to be key to their synergistic dye-releasing activity from lipid vesicles at high concentrations.STATEMENT OF SIGNIFICANCEWe demonstrate that specific interactions of the antimicrobial peptides MG2a and PGLa with each other in POPE/POPG bilayers lead to the formation of surface-aligned parallel dimers, which provide already at low peptide concentrations the nucleus for the peptides’ well-known synergistic activity.

scholarly journals Magainin 2 and PGLa in Bacterial Membrane Mimics II: Membrane Fusion and Sponge Phase Formation

2019 ◽  
Author(s):  
Ivo Kabelka ◽  
Michael Pachler ◽  
Sylvain Prévost ◽  
Ilse Letofsky-Papst ◽  
Karl Lohner ◽  
...  
Keyword(s):  
Antimicrobial Peptides ◽  
Defect Formation ◽  
Preceding Paper ◽  
Lipid Vesicles ◽  
Synergistic Activity ◽  
Electron Microscopic ◽  
Synergistic Mechanism ◽  
Sponge Phase ◽  
Lipid Aggregates ◽  
Dynamics Simulations

ABSTRACTWe studied the synergistic mechanism of equimolar mixtures of magainin 2 (MG2a) and PGLa in phosphatidylethanolamine/phosphatidylglycerol mimics of Gram-negative cytoplasmic membranes. In a preceding paper [Pachler et al., Biophys. J. 2019 xxx], we reported on the early onset of parallel heterodimer formation of the two antimicrobial peptides already at low concentrations and the resulting defect formation in membranes. Here, we focus on the structures of the peptide/lipid aggregates occurring in the synergistic regime at elevated peptide concentrations. Using a combination of calorimetric, scattering, electron microscopic and in silico techniques, we demonstrate that the two peptides, even if applied individually, transform originally large unilamellar vesicles into multilamellar vesicles, with a collapsed interbilayer spacing resulting from peptide induced adhesion. Interestingly, the adhesion does not lead to a peptide induced lipid separation of charged and charge neutral species. In addition to this behavior, equimolar mixtures of MG2a and PGLa formed surface-aligned fibril-like structures, which induced adhesion zones between the membranes and the formation of transient fusion stalks in molecular dynamics simulations and a coexisting sponge phase observed by small-angle X-ray scattering. The previously reported increased leakage of lipid vesicles of identical composition in the presence of MG2a/PGLa mixtures is therefore related to a peptide-induced cross-linking of bilayers.STATEMENT OF SIGNIFICANCEWe demonstrate that the synergistic activity of the antimicrobial peptides MG2a and PGLa correlates to the formation of surface-aligned fibril-like peptide aggregates, which cause membrane adhesion, fusion and finally the formation of a sponge phase.

Synergistic effects of magainin 2 and PGLa on their heterodimer formation, aggregation, and insertion into the bilayer

RSC Advances ◽  
2015 ◽  
Vol 5 (3) ◽  
pp. 2047-2055 ◽  
Author(s):  
Eol Han ◽  
Hwankyu Lee
Keyword(s):  
Molecular Dynamics ◽  
Antimicrobial Peptides ◽  
Molecular Dynamics Simulations ◽  
Lipid Bilayers ◽  
Synergistic Effects ◽  
Coarse Grained ◽  
Dynamics Simulations ◽  
Coarse Grained Molecular Dynamics

We performed coarse-grained molecular dynamics simulations of antimicrobial peptides PGLa and magainin 2 in lipid bilayers.

scholarly journals Dynamics of vesicle reshaping and scission under osmotic shocks

2020 ◽  
Author(s):  
Christian Vanhille Campos ◽  
Anđela Šarić
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Time Scales ◽  
Osmotic Shock ◽  
Lipid Vesicles ◽  
Coarse Grained ◽  
Shock Absorption ◽  
Bursting Events ◽  
Dynamics Simulations ◽  
Insight Into

We study the effects of osmotic shocks on lipid vesicles via coarse-grained molecular dynamics simulations by explicitly considering the solute in the system. We find that depending on their nature (hypo- or hypertonic) such shocks can lead to bursting events or engulfing of external material into inner compartments, among other morphology transformations. We characterize the dynamics of these processes and observe a separation of time scales between the osmotic shock absorption and the shape relaxation. Our work consequently provides an insight into the dynamics of compartmentalization in vesicular systems as a result of osmotic shocks, which can be of interest in the context of early proto-cell development and proto-cell compartmentalisation.

VISUALIZING SOFT MATTER: MESOSCOPIC SIMULATIONS OF MEMBRANES, VESICLES AND NANOPARTICLES

2007 ◽  
Vol 02 (01) ◽  
pp. 33-55 ◽  
Author(s):  
JULIAN SHILLCOCK ◽  
REINHARD LIPOWSKY
Keyword(s):  
Smart Materials ◽  
Soft Matter ◽  
Dissipative Particle Dynamics ◽  
Lipid Vesicles ◽  
Soft Materials ◽  
Coarse Grained ◽  
Molecular Characteristics ◽  
Dynamics Simulations ◽  
And Behavior ◽  
Mesoscopic Simulations

Biological membranes have properties and behavior that emerge from the propagation of the molecular characteristics of their components across many scales. Artificial smart materials, such as drug delivery vehicles and nanoparticles, often rely on modifying naturally-occurring soft matter, such as polymers and lipid vesicles, so that they possess useful behavior. Mesoscopic simulations allow in silico experiments to be easily and cheaply performed on complex, soft materials requiring as input only the molecular structure of the constituents at a coarse-grained level. They can therefore act as a guide to experimenters prior to performing costly assays. Additionally, mesoscopic simulations provide the only currently feasible window on the length and time scales relevant to important biophysical processes such as vesicle fusion. We describe here recent work using Dissipative Particle Dynamics simulations to explore the structure and behavior of amphiphilic membranes, the fusion of vesicles, and the interactions between rigid nanoparticles and soft surfaces.

scholarly journals Joint small-angle X-ray and neutron scattering data analysis of asymmetric lipid vesicles

2017 ◽  
Vol 50 (2) ◽  
pp. 419-429 ◽  
Author(s):  
Barbara Eicher ◽  
Frederick A. Heberle ◽  
Drew Marquardt ◽  
Gerald N. Rechberger ◽  
John Katsaras ◽  
...  
Keyword(s):  
Density Profile ◽  
Small Angle ◽  
Scattering Length ◽  
Lipid Vesicles ◽  
Computational Effort ◽  
Scattering Data ◽  
Joint Analysis ◽  
Melting Transition ◽  
X Ray ◽  
The Individual

Low- and high-resolution models describing the internal transbilayer structure of asymmetric lipid vesicles have been developed. These models can be used for the joint analysis of small-angle neutron and X-ray scattering data. The models describe the underlying scattering length density/electron density profiles either in terms of slabs or through the so-called scattering density profile, previously applied to symmetric lipid vesicles. Both models yield structural details of asymmetric membranes, such as the individual area per lipid, and the hydrocarbon thickness of the inner and outer bilayer leaflets. The scattering density profile model, however, comes at a cost of increased computational effort but results in greater structural resolution, showing a slightly lower packing of lipids in the outer bilayer leaflet of ∼120 nm diameter palmitoyloleoyl phosphatidylcholine (POPC) vesicles, compared to the inner leaflet. Analysis of asymmetric dipalmitoyl phosphatidylcholine/POPC vesicles did not reveal evidence of transbilayer coupling between the inner and outer leaflets at 323 K, i.e. above the melting transition temperature of the two lipids.

scholarly journals Structure and Formation Mechanism of Antimicrobial Peptides Temporin B- and L-Induced Tubular Membrane Protrusion

2021 ◽  
Vol 22 (20) ◽  
pp. 11015
Author(s):  
Shan Zhang ◽  
Ming Ma ◽  
Zhuang Shao ◽  
Jincheng Zhang ◽  
Lei Fu ◽  
...  
Keyword(s):  
Antimicrobial Peptides ◽  
Morphological Changes ◽  
Membrane Surface ◽  
Coarse Grained ◽  
Tubular Structures ◽  
Membrane Pore ◽  
Anionic Phospholipids ◽  
Bactericidal Activities ◽  
Highly Hydrophobic ◽  
Dynamics Simulations

Temporins are a family of antimicrobial peptides (AMPs) isolated from frog skin, which are very short, weakly charged, and highly hydrophobic. They execute bactericidal activities in different ways from many other AMPs. This work investigated morphological changes of planar bilayer membranes composed of mixed zwitterionic and anionic phospholipids induced by temporin B and L (TB and TL) using all-atom and coarse-grained molecular dynamics simulations. We found that TB and TL fold to α-helices at the membrane surface and penetrate shallowly into the bilayer. These short AMPs have low propensity to induce membrane pore formation but possess high ability to extract lipids out. At relatively high peptide concentrations, the strong hydrophobicity of TB and TL promotes them to aggregate into clusters on the membrane surface. These aggregates attract a large amount of lipids out of the membrane to release compression induced by other dispersed peptides binding to the membrane. The extruded lipids mix evenly with the peptides in the cluster and form tubule-like protrusions. Certain water molecules follow the movement of lipids, which not only fill the cavities of the protrusion but also assist in maintaining the tubular structures. In contrast, the peptide-free leaflet remains intact. The present results unravel distinctive antimicrobial mechanisms of temporins disturbing membranes.

Interaction between charged nanoparticles and vesicles: coarse-grained molecular dynamics simulations

2016 ◽  
Vol 18 (46) ◽  
pp. 31946-31957 ◽  
Author(s):  
Linying Liu ◽  
Jianhua Zhang ◽  
Xiaowei Zhao ◽  
Zheng Mao ◽  
Na Liu ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Surface Charge ◽  
Molecular Dynamics Simulations ◽  
Lipid Vesicles ◽  
Coarse Grained ◽  
Charge Densities ◽  
Charged Nanoparticles ◽  
Dynamics Simulations ◽  
Coarse Grained Molecular Dynamics

Interactions between charged nanoparticles and curved zwitterionic lipid vesicles with different surface charge densities (ρ): insertion, repulsion, adsorption, and penetration.

scholarly journals Decoding the physical principles of two-component biomolecular phase separation

2020 ◽  
Author(s):  
Yaojun Zhang ◽  
Bin Xu ◽  
Benjamin G. Weiner ◽  
Yigal Meir ◽  
Ned S. Wingreen
Keyword(s):  
Phase Separation ◽  
Coarse Grained ◽  
Cellular Functions ◽  
Ratio Effect ◽  
Polymer Properties ◽  
Binding Phase ◽  
Membrane Bound ◽  
Dynamics Simulations ◽  
The Individual ◽  
Physical Principles

Cells possess a multiplicity of non-membrane bound compartments, which form via liquid-liquid phase separation. These condensates assemble and dissolve as needed to enable central cellular functions. One important class of condensates is those composed of two associating polymer species that form one-to-one specific bonds. What are the physical principles that underlie phase separation in such systems? To address this question, we employed coarse-grained molecular dynamics simulations to examine how the phase boundaries depend on polymer valence, stoichiometry, and binding strength. We discovered a striking phenomenon – for sufficiently strong binding, phase separation is suppressed at rational polymer stoichiometries, which we termed the magic-ratio effect. We further developed an analytical dimer-gel theory that confirmed the magic-ratio effect and disentangled the individual roles of polymer properties in shaping the phase diagram. Our work provides new insights into the factors controlling the phase diagrams of biomolecular condensates, with implications for natural and synthetic systems.

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