How cholesterol tilt modulates the mechanical properties of saturated and unsaturated lipid membranes. 2013

George Khelashvili, and Daniel Harries
Department of Physiology and Biophysics, Weill Cornell Medical College, New York, New York 10065, United States. gek2009@med.cornell.edu

Although there have been great advances in understanding the effect of cholesterol on various properties of lipid membranes, its mechanistic role in determining the elasticity of bilayers at the molecular level is not fully resolved. Indeed, to date the molecular mechanisms that drive the experimentally detected differences in properties of saturated and unsaturated lipid bilayers that contain cholesterol remain unclear. By quantifying the cholesterol orientational degrees of freedom from atomistic molecular dynamics simulations of mixed lipid-cholesterol membranes, we address this question from the perspective of cholesterol tilt and splay. Following the fluctuations in orientations of cholesterol and of lipid molecules in simulations, we have extracted tilt and splay moduli both for cholesterol molecules and hydrocarbon lipid tails. This has further allowed us to estimate the contributions of these modes to the response of membranes to elastic deformations. We find that tilt and splay deformations importantly contribute to the overall elasticity of the mixed lipid membranes, and that they can account for the experimentally established differences between the liquid ordered sphingomyelin (SM)/cholesterol bilayers and fluid dioleoylphosphocholine (DOPC)/cholesterol bilayers. These findings underscore the importance of tilt and splay moduli, derived from simulations with relative computational ease, as useful metrics for quantitatively characterizing the mechanical properties of mixed lipid-cholesterol bilayers.

UI MeSH Term Description Entries
D008051 Lipid Bilayers Layers of lipid molecules which are two molecules thick. Bilayer systems are frequently studied as models of biological membranes. Bilayers, Lipid,Bilayer, Lipid,Lipid Bilayer
D010713 Phosphatidylcholines Derivatives of PHOSPHATIDIC ACIDS in which the phosphoric acid is bound in ester linkage to a CHOLINE moiety. Choline Phosphoglycerides,Choline Glycerophospholipids,Phosphatidyl Choline,Phosphatidyl Cholines,Phosphatidylcholine,Choline, Phosphatidyl,Cholines, Phosphatidyl,Glycerophospholipids, Choline,Phosphoglycerides, Choline
D002784 Cholesterol The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. Epicholesterol
D004548 Elasticity Resistance and recovery from distortion of shape.
D056004 Molecular Dynamics Simulation A computer simulation developed to study the motion of molecules over a period of time. Molecular Dynamics Simulations,Molecular Dynamics,Dynamic, Molecular,Dynamics Simulation, Molecular,Dynamics Simulations, Molecular,Dynamics, Molecular,Molecular Dynamic,Simulation, Molecular Dynamics,Simulations, Molecular Dynamics

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