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.
Bibliographical noteFunding Information:
We acknowledge insightful discussions with Harel Weinstein, Ernest Mehler, and Chezy Barenholz. DH acknowledges support from the Israel Science Foundation (grants 1011/07 , 1012/07 ) and the Stephanie Gross intramurial fund . GK is supported by NIH grant U54 GM087519 . Computational resources of the David A. Cofrin Center for Biomedical Information in the HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine are gratefully acknowledged. The Fritz Haber Research Center is supported by Minerva Foundation, Munich, Germany.
- Cholesterol orientation
- Lipid tilt modulus
- Molecular dynamics simulations
- Transitions in liquid crystals