Journal article
Mechanism of Shiga Toxin Clustering on Membranes.
- Pezeshkian W Center for Biomembrane Physics (MEMPHYS), Department of Physics, Chemistry and Pharmacy (FKF), University of Southern Denmark , Campusvej 55, 5230 Odense M, Denmark.
- Gao H Institut Curie, PSL Research University , Chemical Biology of Membranes and Therapeutic Delivery unit, INSERM U 1143, CNRS UMR 3666, 26 rue d'Ulm, 75248 Cedex 05 Paris, France.
- Arumugam S Institut Curie, PSL Research University , Chemical Biology of Membranes and Therapeutic Delivery unit, INSERM U 1143, CNRS UMR 3666, 26 rue d'Ulm, 75248 Cedex 05 Paris, France.
- Becken U Institut Curie, PSL Research University , Chemical Biology of Membranes and Therapeutic Delivery unit, INSERM U 1143, CNRS UMR 3666, 26 rue d'Ulm, 75248 Cedex 05 Paris, France.
- Bassereau P Laboratoire Physico Chimie Curie, Institut Curie, PSL Research University, CNRS UMR16855216 , 75248 Cedex 05 Paris, France.
- Florent JC Institut Curie, PSL Research University , Chemical Biology of Membranes and Therapeutic Delivery unit, INSERM U 1143, CNRS UMR 3666, 26 rue d'Ulm, 75248 Cedex 05 Paris, France.
- Ipsen JH Center for Biomembrane Physics (MEMPHYS), Department of Physics, Chemistry and Pharmacy (FKF), University of Southern Denmark , Campusvej 55, 5230 Odense M, Denmark.
- Johannes L Institut Curie, PSL Research University , Chemical Biology of Membranes and Therapeutic Delivery unit, INSERM U 1143, CNRS UMR 3666, 26 rue d'Ulm, 75248 Cedex 05 Paris, France.
- Shillcock JC Ecole polytechnique fédérale de Lausanne (EPFL) , 1015 Lausanne, Switzerland.
- 2016-12-13
Published in:
- ACS nano. - 2017
Casimir force
clustering
endocytosis
fluctuation-induced force
glycosphingolipid
invagination
lectin
membrane
Cell Membrane
Humans
Nanoparticles
Shiga Toxin
Static Electricity
Trihexosylceramides
English
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.
- Language
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- English
- Open access status
- hybrid
- Identifiers
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- DOI 10.1021/acsnano.6b05706
- PMID 27943675
- Persistent URL
- https://sonar.ch/global/documents/20862
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