Cholesterol Induces Uneven Curvature of Asymmetric Lipid Bilayers

Yesylevskyy, Semen O.; Demchenko, Alexander P.; Kraszewski, Sebastian; Ramseyer, Christophe

doi:10.1155/2013/965230

Cited by 40 publications

(40 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Previous work showed a complex interplay between membrane curvature and cholesterol distribution in lipid bilayers31. Of particular interest, the presence of cholesterol is found to help induce negative membrane curvature32.…”

Section: Resultsmentioning

confidence: 99%

EGFR oligomerization organizes kinase-active dimers into competent signalling platforms

et al. 2016

View full text Add to dashboard Cite

Epidermal growth factor receptor (EGFR) signalling is activated by ligand-induced receptor dimerization. Notably, ligand binding also induces EGFR oligomerization, but the structures and functions of the oligomers are poorly understood. Here, we use fluorophore localization imaging with photobleaching to probe the structure of EGFR oligomers. We find that at physiological epidermal growth factor (EGF) concentrations, EGFR assembles into oligomers, as indicated by pairwise distances of receptor-bound fluorophore-conjugated EGF ligands. The pairwise ligand distances correspond well with the predictions of our structural model of the oligomers constructed from molecular dynamics simulations. The model suggests that oligomerization is mediated extracellularly by unoccupied ligand-binding sites and that oligomerization organizes kinase-active dimers in ways optimal for auto-phosphorylation in trans between neighbouring dimers. We argue that ligand-induced oligomerization is essential to the regulation of EGFR signalling.

show abstract

Section: Resultsmentioning

confidence: 99%

EGFR oligomerization organizes kinase-active dimers into competent signalling platforms

et al. 2016

View full text Add to dashboard Cite

show abstract

“…Coarse-grain simulations of vesicle fusion are critical because they have been shown to not only correlate with experimental studies but also fill the gaps left by them. Likewise, the Martini force field has been commonly used to probe membrane topology changes governed by membrane composition (35), cholesterol distribution (36), and influenza hemagglutinin fusion peptides (34). Additionally, the effect of membrane of curvature on plasma membrane lipid sorting (76) and packing (77) has been studied.…”

Section: Discussionmentioning

confidence: 99%

“…In this study, we have performed coarse-grain molecular dynamics simulations to probe the cav-1-membrane interactions and dissect the role of cholesterol, palmitoyl tail, and conformational dynamics. The Martini force field has been commonly used to probe membrane topology changes in membrane fusion (34), membrane composition (35), and cholesterol distribution (36). Coarse-grain simulations of vesicle fusion and curvature were critical as they were shown to not only correlate with experimental studies but also fill the gaps left by them (37).…”

Section: Introductionmentioning

confidence: 99%

Interplay between Membrane Curvature and Cholesterol: Role of Palmitoylated Caveolin-1

Krishna

Sengupta

2019

Biophysical Journal

View full text Add to dashboard Cite

Caveolin-1 (cav-1) is an important player in cell signaling and endocytosis that has been shown to colocalize with cholesterol-rich membrane domains. Experimental studies with varying cav-1 constructs have suggested that it can induce both cholesterol clustering and membrane curvature. Here, we probe the molecular origin of membrane curvature and cholesterol clustering by cav-1 by using coarse-grain molecular dynamics simulations. We have performed a series of simulations of a functionally important cav-1 construct, comprising the membrane-interacting domains and a C-terminal palmitoyl tail. Our results suggest that cav-1 is able to induce cholesterol clustering in the membrane leaflet to which it is bound as well as the opposing leaflet. A positive membrane curvature is observed upon cav-1 binding in cholesterol-containing bilayers. Interestingly, we observe an interplay between cholesterol clustering and membrane curvature such that cav-1 is able to induce higher membrane curvature in cholesterol-rich membranes. The role of the cav-1 palmitoyl tail is less clear and appears to increase the membrane contacts. Further, we address the importance of the secondary structure of cav-1 domains and show that it could play an important role in membrane curvature and cholesterol clustering. Our work is an important step toward a molecular picture of caveolae and vesicular endocytosis.

show abstract

“…Furthermore, clustering of cholesterol into lipid rafts was observed in the outer membrane of B. burgdorferi. As cholesterol promotes curvature in asymmetrical bilayers 99 , these raft regions could be favoured for OMV biogenesis. Similar observations have been made for H. pylori 100 , but it remains to be determined whether the involvement of OMVs in this two-way lipid exchange is frequently used by other bacteria.…”

Section: Omv Functions In Bacterial Physiologymentioning

confidence: 99%

Outer-membrane vesicles from Gram-negative bacteria: biogenesis and functions

2015

View full text Add to dashboard Cite

Outer-membrane vesicles (OMVs) are spherical buds of the outer membrane filled with periplasmic content and are commonly produced by Gram-negative bacteria. The production of OMVs allows bacteria to interact with their environment, and OMVs have been found to mediate diverse functions, including promoting pathogenesis, enabling bacterial survival during stress conditions and regulating microbial interactions within bacterial communities. Additionally, because of this functional versatility, researchers have begun to explore OMVs as a platform for bioengineering applications. In this Review, we discuss recent advances in the study of OMVs, focusing on new insights into the mechanisms of biogenesis and the functions of these vesicles.

show abstract

Cholesterol Induces Uneven Curvature of Asymmetric Lipid Bilayers

Cited by 40 publications

References 48 publications

EGFR oligomerization organizes kinase-active dimers into competent signalling platforms

EGFR oligomerization organizes kinase-active dimers into competent signalling platforms

Interplay between Membrane Curvature and Cholesterol: Role of Palmitoylated Caveolin-1

Outer-membrane vesicles from Gram-negative bacteria: biogenesis and functions

Contact Info

Product

Resources

About