Caveolin induced membrane curvature and lipid clustering: two sides of the same coin?

TitleCaveolin induced membrane curvature and lipid clustering: two sides of the same coin?
Publication TypeJournal Article
Year of Publication2021
AuthorsPrakash, S, Krishna, A, Sengupta, D
JournalFaraday Discussions
Volume232
Pagination218-235
Date PublishedDEC
Type of ArticleArticle
ISSN1359-6640
AbstractCaveolin-1 (cav-1) is a multi-domain membrane protein that is a key player in cell signaling, endocytosis and mechanoprotection. It is the principle component of cholesterol-rich caveolar domains and has been reported to induce membrane curvature. The molecular mechanisms underlying the interactions of cav-1 with complex membranes, leading to modulation of membrane topology and the formation of cholesterol-rich domains, remain elusive. In this study, we aim to understand the effect of lipid composition by analyzing the interactions of cav-1 with complex membrane bilayers comprised of about sixty lipid types. We have performed a series of coarse-grain molecular dynamics simulations using the Martini force-field with a cav-1 protein construct (residue 82-136) that includes the membrane binding domains and a palmitoyl tail. We observe that cav-1 induces curvature in this complex membrane, though it is restricted to a nanometer length scale. Concurrently, we observe a clustering of cholesterol, sphingolipids and other lipid molecules leading to the formation of nanodomains. Direct microsecond timescale interactions are observed for specific lipids such as cholesterol, phosphatidylserine and phosphatidylethanolamine lipid types. The results indicate that there is an interplay between membrane topology and lipid species. Our work is a step toward understanding how lipid composition and organization regulate the formation of caveolae, in the context of endocytosis and cell signaling.
DOI10.1039/d0fd00062k
Type of Journal (Indian or Foreign)Foreign
Impact Factor (IF)4.008
Divison category: 
Physical and Materials Chemistry

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