The effects of globotriaosylceramide tail saturation level on bilayer phases

Pezeshkian, Weria; Chaban, Vitaly V.; Johannes, Ludger; Shillcock, Julian C.; Ipsen, John Hjort; Khandelia, Himanshu

doi:10.1039/c4sm02456g

Cited by 21 publications

(27 citation statements)

References 47 publications

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“…They further speculated that unsaturated Gb3 species may be the essential ones for Gb3 concentrations [106], which would be in accordance to the described findings facilitating lipid compaction.…”

Section: Accepted Manuscriptsupporting

confidence: 61%

How synthetic membrane systems contribute to the understanding of lipid-driven endocytosis

Schubert

Römer

2015

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

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Synthetic membrane systems, such as giant unilamellar vesicles and solid supported lipid bilayers, have widened our understanding of biological processes occurring at or through membranes. Artificial systems are particularly suited to study the inherent properties of membranes with regard to their components and characteristics. This review critically reflects the emerging molecular mechanism of lipid-driven endocytosis and the impact of model membrane systems in elucidating the complex interplay of biomolecules within this process. Lipid receptor clustering induced by binding of several toxins, viruses and bacteria to the plasma membrane leads to local membrane bending and formation of tubular membrane invaginations. Here, lipid shape, and protein structure and valency are the essential parameters in membrane deformation. Combining observations of complex cellular processes and their reconstitution on minimal systems seems to be a promising future approach to resolve basic underlying mechanisms. This article is part of a Special Issue entitled: Mechanobiology.

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Section: Accepted Manuscriptsupporting

confidence: 61%

How synthetic membrane systems contribute to the understanding of lipid-driven endocytosis

Schubert

Römer

2015

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

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“…Description of the thermal Casimir force between membrane inclusions as presented in the literature and our calculations using the proximity force approximation of the thermal Casimir force between a pair of polygonal particles at separations that are small compared to their size, the dissipative particle dynamics simulations of nanoparticles adsorbed to a fluctuating membrane, showing that only when the nanoparticles suppress the membrane fluctuations do they experience a clustering force, reanalysis of trajectories from our previously published molecular dynamics (MD) simulations 14,18 showing that the binding of STxB to the membrane does not change the lipids’ chain order parameter nor their rotational diffusion, experimental protocol for adding the STxB toxin particles to the vesicles and cells, estimation of the membrane coverage due to STxB binding to Gb3 lipids, FCS experiments that are used to measure the decrease in diffusion as the toxin nanoparticles aggregate, and complete organic synthesis reactions for the PEG-modified Gb3 lipids (PDF)…”

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confidence: 99%

Mechanism of Shiga Toxin Clustering on Membranes

et al. 2016

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The bacterial Shiga toxin interacts with its cellular receptor, the glycosphingolipid globotriaosylceramide (Gb3 or CD77), as a first step to entering target cells. Previous studies have shown that toxin molecules cluster on the plasma membrane, despite the apparent lack of direct interactions between them. The precise mechanism by which this clustering occurs remains poorly defined. Here, we used vesicle and cell systems and computer simulations to show that line tension due to curvature, height, or compositional mismatch, and lipid or solvent depletion cannot drive the clustering of Shiga toxin molecules. By contrast, in coarse-grained computer simulations, a correlation was found between clustering and toxin nanoparticle-driven suppression of membrane fluctuations, and experimentally we observed that clustering required the toxin molecules to be tightly bound to the membrane surface. The most likely interpretation of these findings is that a membrane fluctuation-induced force generates an effective attraction between toxin molecules. Such force would be of similar strength to the electrostatic force at separations around 1 nm, remain strong at distances up to the size of toxin molecules (several nanometers), and persist even beyond. This force is predicted to operate between manufactured nanoparticles providing they are sufficiently rigid and tightly bound to the plasma membrane, thereby suggesting a route for the targeting of nanoparticles to cells for biomedical applications.

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“…3, C and D) compared to Gb 3 -S. In general, formation of membrane invaginations occurs in three steps: 1) protein binding to the membrane, 2) line tension-driven formation of STxB-Gb 3 aggregates, and 3) generation of negative curvature leading to invaginations (protein cluster formation alone is not sufficient to induce membrane invaginations) (2). If saturated fatty acids are attached to Gb 3 , protein clusters are observed; however, invaginations in GUVs do not form, while unsaturated fatty acids facilitate membrane bending (1,20), which might be a result of the reduced lipid packing order (20). We found that subtle variations of the Gb 3 molecules such as chirality substantially changes protein/membrane organization, which in turn acts on the propensity of tubule formation in membranes.…”

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confidence: 96%

2-Hydroxy Fatty Acid Enantiomers of Gb 3 Impact Shiga Toxin Binding and Membrane Organization

Schütte

Patalag

Weber

et al. 2015

Biophysical Journal

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Shiga toxin subunit B (STxB) binding to its cellular receptor Gb3 leads to the formation of protein-lipid clusters and bending of the membrane. A newly developed synthetic route allowed synthesizing the biologically most relevant Gb3-C24:1 2OH species with both, the natural (Gb3-R) as well as the unnatural (Gb3-S) configuration of the 2OH group. The derivatives bind STxB with identical nanomolar affinity, while the propensity to induce membrane tubules in giant unilamellar vesicles is more pronounced for Gb3-S. Fluorescence and atomic force microscopy images of phase-separated supported membranes revealed differences in the lateral organization of the protein on the membrane. Gb3-R favorably induces large and tightly packed protein clusters, while a lower protein density is found on Gb3-S doped membranes.

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The effects of globotriaosylceramide tail saturation level on bilayer phases

Cited by 21 publications

References 47 publications

How synthetic membrane systems contribute to the understanding of lipid-driven endocytosis

How synthetic membrane systems contribute to the understanding of lipid-driven endocytosis

Mechanism of Shiga Toxin Clustering on Membranes

2-Hydroxy Fatty Acid Enantiomers of Gb 3 Impact Shiga Toxin Binding and Membrane Organization

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