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Interleaflet Decoupling in a Lipid Bilayer at Excess Cholesterol Probed by Spectroscopic Ellipsometry and Simulations

Kamble, Sagar ; Patil, Snehal ; Kulkarni, Mandar LU and Appala, Venkata Ramana Murthy (2020) In Journal of Membrane Biology 253(6). p.647-659
Abstract

Abstract: Artificial lipid membranes are often investigated as a replica of the cell membrane in the form of supported lipid bilayers (SLBs). In SLBs, the phase state of a lipid bilayer strongly depends on the presence of molecules such as cholesterol, ceramide, and physical parameters such as temperature. Cholesterol is a key molecule of biological membranes and it exerts condensing effect on lipid bilayers. In this paper, we demonstrate the influence of excess cholesterol content on a supported lipid bilayer of 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) (fluid-phase) using spectroscopic ellipsometry (SE) and coarse-grained (CG) molecular dynamics (MD) simulations. The results show the condensation effect due to cholesterol... (More)

Abstract: Artificial lipid membranes are often investigated as a replica of the cell membrane in the form of supported lipid bilayers (SLBs). In SLBs, the phase state of a lipid bilayer strongly depends on the presence of molecules such as cholesterol, ceramide, and physical parameters such as temperature. Cholesterol is a key molecule of biological membranes and it exerts condensing effect on lipid bilayers. In this paper, we demonstrate the influence of excess cholesterol content on a supported lipid bilayer of 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) (fluid-phase) using spectroscopic ellipsometry (SE) and coarse-grained (CG) molecular dynamics (MD) simulations. The results show the condensation effect due to cholesterol addition up to 30% and interleaflet decoupling at excess cholesterol beyond 30%. SE results show the separation of individual leaflets of the bilayer and influence of cholesterol on the biophysical properties such as thickness and optical index. CG simulations were performed at different ratios of DOPC:cholesterol mixtures to explore cholesterol-driven bilayer properties and stability. The simulations displayed the accumulation of cholesterol molecules at the interface of the lower and upper leaflets of the bilayer, thus leading to undulations in the bilayer. This work reports the successful application of SE technique to study lipid–cholesterol interactions for the first time. Graphical abstract: [Figure not available: see fulltext.].

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author
; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Cholesterol, Coarse-grained simulations, DOPC, Lipid membranes, MARTINI force field, Spectroscopic ellipsometry
in
Journal of Membrane Biology
volume
253
issue
6
pages
13 pages
publisher
Springer
external identifiers
  • scopus:85096314146
  • pmid:33221946
ISSN
0022-2631
DOI
10.1007/s00232-020-00156-9
language
English
LU publication?
yes
id
9591aa90-0ae5-43d1-8f86-378e6986d385
date added to LUP
2020-12-02 11:29:02
date last changed
2024-05-16 00:02:01
@article{9591aa90-0ae5-43d1-8f86-378e6986d385,
  abstract     = {{<p>Abstract: Artificial lipid membranes are often investigated as a replica of the cell membrane in the form of supported lipid bilayers (SLBs). In SLBs, the phase state of a lipid bilayer strongly depends on the presence of molecules such as cholesterol, ceramide, and physical parameters such as temperature. Cholesterol is a key molecule of biological membranes and it exerts condensing effect on lipid bilayers. In this paper, we demonstrate the influence of excess cholesterol content on a supported lipid bilayer of 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) (fluid-phase) using spectroscopic ellipsometry (SE) and coarse-grained (CG) molecular dynamics (MD) simulations. The results show the condensation effect due to cholesterol addition up to 30% and interleaflet decoupling at excess cholesterol beyond 30%. SE results show the separation of individual leaflets of the bilayer and influence of cholesterol on the biophysical properties such as thickness and optical index. CG simulations were performed at different ratios of DOPC:cholesterol mixtures to explore cholesterol-driven bilayer properties and stability. The simulations displayed the accumulation of cholesterol molecules at the interface of the lower and upper leaflets of the bilayer, thus leading to undulations in the bilayer. This work reports the successful application of SE technique to study lipid–cholesterol interactions for the first time. Graphical abstract: [Figure not available: see fulltext.].</p>}},
  author       = {{Kamble, Sagar and Patil, Snehal and Kulkarni, Mandar and Appala, Venkata Ramana Murthy}},
  issn         = {{0022-2631}},
  keywords     = {{Cholesterol; Coarse-grained simulations; DOPC; Lipid membranes; MARTINI force field; Spectroscopic ellipsometry}},
  language     = {{eng}},
  number       = {{6}},
  pages        = {{647--659}},
  publisher    = {{Springer}},
  series       = {{Journal of Membrane Biology}},
  title        = {{Interleaflet Decoupling in a Lipid Bilayer at Excess Cholesterol Probed by Spectroscopic Ellipsometry and Simulations}},
  url          = {{http://dx.doi.org/10.1007/s00232-020-00156-9}},
  doi          = {{10.1007/s00232-020-00156-9}},
  volume       = {{253}},
  year         = {{2020}},
}