Interplay of Unsaturated Phospholipids and Cholesterol in Membranes: Effect of the Double-Bond Position

Abstract

The structural and dynamical properties of lipid membranes rich in phospholipids and cholesterol are known to be strongly affected by the unsaturation of lipid acyl chains. We show that not only unsaturation but also the position of a double bond has a pronounced effect on membrane properties. We consider how cholesterol interacts with phosphatidylcholines comprising two 18-carbon long monounsaturated acyl chains, where the position of the double bond is varied systematically along the acyl chains. Atomistic molecular dynamics simulations indicate that when the double bond is not in contact with the cholesterol ring, and especially with the C18 group on its rough beta-side, the membrane properties are closest to those of the saturated bilayer. However, any interaction between the double bond and the ring promotes membrane disorder and fluidity. Maximal disorder is found when the double bond is located in the middle of a lipid acyl chain, the case most commonly found in monounsaturated acyl chains of phospholipids. The results suggest a cholesterol-mediated lipid selection mechanism in eukaryotic cell membranes. With saturated lipids, cholesterol promotes the formation of highly ordered raft-like membrane domains, whereas domains rich in unsaturated lipids with a double bond in the middle remain highly fluid despite the presence of cholesterol.

Inhibitory effect of dietary lipids on chaperone-mediated autophagy

“…In contrast, other changes may help to maintain the fluidity of the membrane outside the microdomain regions despite the high increase in cholesterol. For example, the observed switch toward unsaturated forms of SM and CER would allow for such high concentrations of cholesterol while maintaining fluidity, because unsaturated lipids with a double bond in the middle of the acyl chain remain fluid even in the presence of cholesterol (37).…”

Recent development in computer simulations of lipid bilayers

“…Such 221 , for eight different PC bilayer systems with 20 mol % CHOL comprising two 18-carbon long monounsaturated acyl chains, where the position of the cis double bond is varied systematically along the acyl chains, namely 18:0/18:0 PC, 18:1(n-3)cis/18:1(n-3)cis PC, 18:1(n-5)cis/18:1(n-5)cis PC, 18:1(n-7)cis/18:1(n-7)cis PC, 18:1(n-9)cis/18:1(n-9)cis PC, 18:1(n-11)cis/18:1(n-11)cis PC, 18:1(n-13)cis/18:1(n-13)cis PC, and 18:1(n-15)cis/18:1(n-15)cis PC 134,135 .…”

“…They are assessable experimentally by the NMR technique. The bond ordering in various phospholipid and phospholipid/CHOL bilayers have been studied repeatedly within recent years by computer simulation methods 56,57,61,81,93,109,115,121,122,[126][127][128][129][130][131][132]134,136,137,139,141,143,[213][214][215][216][217][218][219][220][221] .…”

Live-Cell TIRF Imaging of Molecular Assembly and Plasma Membrane Topography

“…The complexity of the membrane lipid composition has suggested the coexistence of domains characterized by different dynamic properties in the membrane plane as sites for preferential partitioning of proteins and solutes, for modulating membrane activity, and for diffusion along the plane and through the bilayer. [24][25][26][27][28][29][30][31][32][33] Several invasive methods that use membrane isolation can be used to establish the exact lipid composition of membranes. However, when these methods are used to study membrane domains, they can be subject to localization error because lipids can migrate between different cellular compartments during the membrane isolation.…”