Molecular origins of bending rigidity in lipids with isolated and conjugated double bonds: The effect of cholesterol

G. Khelashvili*, N. Johner, G. Zhao, D. Harries, H. L. Scott

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

We examine the effects of cholesterol (Chol) on the mechanical properties of membranes consisting of 16:0/18:1 POPC lipid and of lipids with conjugated linoleic acid (CLA), cis-9/trans-11 CLA (C9T11) and trans-10/cis-12 CLA (T10C12). Atomistic molecular dynamics (MD) simulations of POPC-Chol and CLA-Chol mixtures at various Chol concentrations are employed within a recently developed and validated computational methodology (Khelashvili et al., 2013) that calculates from MD trajectories the bending rigidity (KC) for these systems. We have found that the addition of 30% Chol stiffens POPC lipid membranes much more significantly (2.3-fold) than it does C9T11 (1.5-fold) or T10C12 (1.75-fold) lipid bilayers. Extensive comparative structural analysis of the simulated mixtures supports a molecular mechanism for the differential effects of cholesterol, whereby the sterol molecules tilt more significantly in CLA membranes where they also insert deeper inside the hydrocarbon core. The observed distinct arrangement of Chol molecules in CLA and POPC bilayers, in turn, is dictated by the interplay between the specific location of the trans double bond in the two CLA lipid isomers and the preferential interaction of the rigid Chol ring with the saturated segments of the lipid tails. The simulations and analysis described in this paper provide novel insights into the specific modes of molecular interaction in bilayers composed of mixtures of Chol and unsaturated lipids that drive emergent macroscopic properties, such as the membrane's bending modulus.

Original languageAmerican English
Pages (from-to)18-26
Number of pages9
JournalChemistry and Physics of Lipids
Volume178
DOIs
StatePublished - Feb 2014

Bibliographical note

Funding Information:
G.K. and N.J. are supported by HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute of Computational Biomedicine at Weill Medical College of Cornell University . G.Z is supported by Biomedical Engineering Cross Research Fund of Shanghai Jiao Tong University ( YG2012MS23 ) and Natural Science Foundation Program at Shanghai Jiao Tong University School of Medicine ( 12XJ10078 ).

Keywords

  • Bending rigidity
  • Cholesterol
  • Conjugated linoleic acids
  • Lipid splay and tilt
  • Molecular dynamic simulation
  • POPC

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