Cholesterol-induced suppression of membrane elastic fluctuations at the atomistic level

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• 作者：Trivikram R. Molugu^a ; Michael F. Brown^a ; ^b ; ^{mfbrown@u.arizona.edu" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Solid-state NMR ; Area per lipid ; Cholesterol ; Lanosterol ; Membrane elasticity ; Lipid rafts
• 刊名：Chemistry and Physics of Lipids
• 出版年：2016
• 出版时间：September 2016
• 年：2016
• 卷：199
• 期：Complete
• 页码：39-51
• 全文大小：2257 K

文摘

Applications of solid-state NMR spectroscopy for investigating the influences of lipid-cholesterol interactions on membrane fluctuations are reviewed in this paper. Emphasis is placed on understanding the energy landscapes and fluctuations at an emergent atomistic level. Solid-state ²H NMR spectroscopy directly measures residual quadrupolar couplings (RQCs) due to individual C–²H labeled segments of the lipid molecules. Moreover, residual dipolar couplings (RDCs) of ¹³C–¹H bonds are obtained in separated local-field NMR spectroscopy. The distributions of RQC or RDC values give nearly complete profiles of the order parameters as a function of acyl segment position. Measured equilibrium properties of glycerophospholipids and sphingolipids including their binary and tertiary mixtures with cholesterol show unequal mixing associated with liquid-ordered domains. The entropic loss upon addition of cholesterol to sphingolipids is less than for glycerophospholipids and may drive the formation of lipid rafts. In addition relaxation time measurements enable one to study the molecular dynamics over a wide time-scale range. For ²H NMR the experimental spin-lattice (R_1Z) relaxation rates follow a theoretical square-law dependence on segmental order parameters (S_CD) due to collective slow dynamics over mesoscopic length scales. The functional dependence for the liquid-crystalline lipid membranes is indicative of viscoelastic properties as they emerge from atomistic-level interactions. A striking decrease in square-law slope upon addition of cholesterol denotes stiffening relative to the pure lipid bilayers that is diminished in the case of lanosterol. Measured equilibrium properties and relaxation rates infer opposite influences of cholesterol and detergents on collective dynamics and elasticity at an atomistic scale that potentially affects lipid raft formation in cellular membranes.