title: Cholesterol-induced suppression of membrane elastic fluctuations at the atomistic level.
abstract: 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 (2)H NMR spectroscopy directly measures residual quadrupolar couplings (RQCs) due to individual C-(2)H labeled segments of the lipid molecules. Moreover, residual dipolar couplings (RDCs) of (13)C-(1)H 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 (2)H NMR the experimental spin-lattice (R1Z) relaxation rates follow a theoretical square-law dependence on segmental order parameters (SCD) 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.
authors.affiliation: Department of Chemistry and Biochemistry, University of Arizona, Tucson, AZ 85721, USA.
authors.forename: Trivikram R
authors.initials: TR
authors.lastname: Molugu
authors.affiliation: Department of Chemistry and Biochemistry, University of Arizona, Tucson, AZ 85721, USA; Department of Physics, University of Arizona, Tucson, AZ 85721, USA. Electronic address: mfbrown@u.arizona.edu.
authors.forename: Michael F
authors.initials: MF
authors.lastname: Brown
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000737:chemistry* / Q000378:metabolism*; D002784:Cholesterol / Q000737:chemistry* / Q000378:metabolism*; D004548:Elasticity; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*
chemical_list: D002784:Cholesterol
keywords: Area per lipid; Cholesterol; Lanosterol; Lipid rafts; Membrane elasticity; Solid-state NMR