Mechanism of Shiga Toxin Clustering on Membranes
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Standard
Mechanism of Shiga Toxin Clustering on Membranes. / Pezeshkian, Weria; Gao, Haifei; Arumugam, Senthil; Becken, Ulrike; Bassereau, Patricia; Florent, Jean-Claude; Ipsen, John Hjort; Johannes, Ludger; Shillcock, Julian C.
I: ACS Nano, Bind 11, Nr. 1, 01.01.2017, s. 314-324.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - Mechanism of Shiga Toxin Clustering on Membranes
AU - Pezeshkian, Weria
AU - Gao, Haifei
AU - Arumugam, Senthil
AU - Becken, Ulrike
AU - Bassereau, Patricia
AU - Florent, Jean-Claude
AU - Ipsen, John Hjort
AU - Johannes, Ludger
AU - Shillcock, Julian C.
PY - 2017/1/1
Y1 - 2017/1/1
N2 - 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.
AB - 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.
KW - Casimir force
KW - fluctuation-induced force
KW - endocytosis
KW - invagination
KW - membrane
KW - clustering glycosphingolipid
KW - lectin
KW - FLUCTUATION-INDUCED INTERACTIONS
KW - MEDIATED INTERACTIONS
KW - LIPID INTERACTIONS
KW - FLUID MEMBRANES
KW - INDUCED FORCES
KW - INCLUSIONS
KW - CURVATURE
KW - CELLS
KW - ATTRACTION
KW - INTERFACES
U2 - 10.1021/acsnano.6b05706
DO - 10.1021/acsnano.6b05706
M3 - Journal article
VL - 11
SP - 314
EP - 324
JO - A C S Nano
JF - A C S Nano
SN - 1936-0851
IS - 1
ER -
ID: 316868047