title: How sterol tilt regulates properties and organization of lipid membranes and membrane insertions.
abstract: Serving as a crucial component of mammalian cells, cholesterol critically regulates the functions of biomembranes. This review focuses on a specific property of cholesterol and other sterols: the tilt modulus χ that quantifies the energetic cost of tilting sterol molecules inside the lipid membrane. We show how χ is involved in determining properties of cholesterol-containing membranes, and detail a novel approach to quantify its value from atomistic molecular dynamics (MD) simulations. Specifically, we link χ with other structural, thermodynamic, and mechanical properties of cholesterol-containing lipid membranes, and delineate how this useful parameter can be obtained from the sterol tilt probability distributions derived from relatively small-scale unbiased MD simulations. We demonstrate how the tilt modulus quantitatively describes the aligning field that sterol molecules create inside the phospholipid bilayers, and we relate χ to the bending rigidity of the lipid bilayer through effective tilt and splay energy contributions to the elastic deformations. Moreover, we show how χ can conveniently characterize the "condensing effect" of cholesterol on phospholipids. Finally, we demonstrate the importance of this cholesterol aligning field to the proper folding and interactions of membrane peptides. Given the relative ease of obtaining the tilt modulus from atomistic simulations, we propose that χ can be routinely used to characterize the mechanical properties of sterol/lipid bilayers, and can also serve as a required fitting parameter in multi-scaled simulations of lipid membrane models to relate the different levels of coarse-grained details.
authors.affiliation: Department of Physiology and Biophysics, Weill Medical College of Cornell University, 1300 York Avenue, Room LC-501B, New York, NY, USA. gek2009@med.cornell.edu
authors.forename: George
authors.initials: G
authors.lastname: Khelashvili
authors.forename: Daniel
authors.initials: D
authors.lastname: Harries
mesh_terms: D002462:Cell Membrane / Q000378:metabolism*; D050356:Lipid Metabolism; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism; D013261:Sterols / Q000737:chemistry* / Q000378:metabolism*; D013816:Thermodynamics
chemical_list: D008565:Membrane Proteins; D013261:Sterols