Molecular Mechanism of Cyclodextrin Mediated Cholesterol Extraction

Molecular Mechanism of Cyclodextrin Mediated Cholesterol Extraction

The depletion of cholesterol from membranes, mediated by β-cyclodextrin (β-CD) is well known and documented, but the molecular details of this process are largely unknown. Using molecular dynamics simulations, we have been able to study the CD mediated extraction of cholesterol from model membranes, in particular from a pure cholesterol monolayer, at atomic resolution. Our results show that eff...

University of Groningen Computational microscopy of cyclodextrin mediated cholesterol extraction from lipid model membranes

Computational microscopy of cyclodextrin mediated cholesterol extraction from lipid model membranes

Beta-cyclodextrins (β-CDs) can form inclusion complexes with cholesterol, and are commonly used to manipulate cholesterol levels of biomembranes. In this work, we have used multiscale molecular dynamics simulations to provide a detailed view on the interaction between β-CDs and lipid model membranes. We show that cholesterol can be extracted efficiently upon adsorption of β-CD dimers at the mem...

Molecular mechanism of cholesterol- and polyphosphoinositide-mediated syntaxin clustering.

The neuronal acceptor SNARE complex that functions as the receptor for synaptic vesicle docking and fusion at the presynaptic membrane is composed of the single-span transmembrane protein syntaxin-1A and the palmitoylated soluble protein SNAP-25. Previously, we explored interactions that promote the formation of syntaxin-1A clusters in membranes. Cholesterol activates clustering in native and m...

Extraction of cholesterol with methyl-beta-cyclodextrin perturbs formation of clathrin-coated endocytic vesicles.

The importance of cholesterol for endocytosis has been investigated in HEp-2 and other cell lines by using methyl-beta-cyclodextrin (MbetaCD) to selectively extract cholesterol from the plasma membrane. MbetaCD treatment strongly inhibited endocytosis of transferrin and EGF, whereas endocytosis of ricin was less affected. The inhibition of transferrin endocytosis was completely reversible. On r...