Mechanism of Shiga Toxin Clustering on Membranes
| Autor: | Weria Pezeshkian, Senthil Arumugam, John Hjort Ipsen, Ludger Johannes, Ulrike Becken, Patricia Bassereau, Julian C. Shillcock, Haifei Gao, Jean-Claude Florent |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Casimir force invagination Static Electricity Cell Globotriaosylceramide General Physics and Astronomy 02 engineering and technology medicine.disease_cause Article Shiga Toxin 03 medical and health sciences chemistry.chemical_compound medicine Humans endocytosis General Materials Science Cluster analysis membrane Glyocsphingolipid biology glycosphingolipid Chemistry Toxin Trihexosylceramides Vesicle Cell Membrane General Engineering Shiga toxin Glycosphingolipid 021001 nanoscience & nanotechnology fluctuation-induced force Membrane clustering 030104 developmental biology Membrane medicine.anatomical_structure Biochemistry biology.protein Biophysics Nanoparticles lectin Additions and Corrections 0210 nano-technology clustering |
| Zdroj: | ACS Nano Pezeshkian, W, Gao, H, Arumugam, S, Becken, U, Bassereau, P, Florent, J C, Ipsen, J H, Johannes, L & Shillcock, J C 2017, ' Mechanism of Shiga Toxin Clustering on Membranes ', ACS Nano, vol. 11, no. 1, pp. 314-324 . https://doi.org/10.1021/acsnano.6b05706 |
| ISSN: | 1936-086X 1936-0851 |
| DOI: | 10.1021/acsnano.6b05706 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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