02094nas a2200169   4500008004100000022001400041245009000055210006900145260000800214300001200222490000800234520150600242100002001748700002001768700002001788856011601808       2021                        eng d  a1359-664000aCaveolin induced membrane curvature and lipid clustering: two sides of the same coin?0 aCaveolin induced membrane curvature and lipid clustering two sid  cDEC  a218-2350 v2323 aCaveolin-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.1 aPrakash, Shikha1 aKrishna, Anjali1 aSengupta, Durba  uhttps://library.ncl.res.in/content/caveolin-induced-membrane-curvature-and-lipid-clustering-two-sides-same-coin