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Title: Cholesterol Flip-Flop Impacts Domain Registration in Plasma Membrane Models

Abstract

The plasma membrane is a highly complex multicomponent system that is central to the functioning of cells. Cholesterol, a key lipid component of the plasma membrane, promotes the formation of nanodomains. These nanodomains are often correlated across the two membrane leaflets, but the underlying physical mechanism remains unclear. Using coarse-grained molecular dynamics simulations, we investigate the influence of cholesterol flip-flop on membrane properties, in particular, the interleaflet coupling of cholesterol-enriched domains. We show that the cholesterol density correlation between the leaflets of an average mammalian plasma membrane is significantly reduced by suppressing interleaflet cholesterol population. Our results suggest an amplifying role of cholesterol in signal transduction across the leaflets.

Authors:
ORCiD logo [1]; ORCiD logo [2];  [1]
+ Show Author Affiliations
  1. Univ. of Groningen, Groningen (Netherlands). Groningen Biomolecular Sciences and Biotechnology Inst. and The Zernike Inst. for Advanced Material
  2. Univ. of Groningen, Groningen (Netherlands). Groningen Biomolecular Sciences and Biotechnology Inst. and The Zernike Inst. for Advanced Material; Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States). Biosciences and Biotechnology Division, Physical and Life Sciences Directorate
Publication Date:
Research Org.:
Lawrence Livermore National Laboratory (LLNL), Livermore, CA (United States); Univ. of Groningen, Groningen (Netherlands). Faculty of Mathematics and Natural Sciences
Sponsoring Org.:
USDOE National Nuclear Security Administration (NNSA); USDOE Office of Science (SC), Basic Energy Sciences (BES)
OSTI Identifier:
1488792
Alternate Identifier(s):
OSTI ID: 1508623
Report Number(s):
LLNL-JRNL-751356
Journal ID: ISSN 1948-7185; 937164
Grant/Contract Number:  
AC52-07NA27344
Resource Type:
Accepted Manuscript
Journal Name:
Journal of Physical Chemistry Letters
Additional Journal Information:
Journal Volume: 9; Journal Issue: 18; Journal ID: ISSN 1948-7185
Publisher:
American Chemical Society
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES

Citation Formats

Thallmair, Sebastian, Ingólfsson, Helgi I., and Marrink, Siewert J. Cholesterol Flip-Flop Impacts Domain Registration in Plasma Membrane Models. United States: N. p., 2018. Web. doi:10.1021/acs.jpclett.8b01877.
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Thallmair, Sebastian, Ingólfsson, Helgi I., & Marrink, Siewert J. Cholesterol Flip-Flop Impacts Domain Registration in Plasma Membrane Models. United States. https://doi.org/10.1021/acs.jpclett.8b01877
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Thallmair, Sebastian, Ingólfsson, Helgi I., and Marrink, Siewert J. Fri . "Cholesterol Flip-Flop Impacts Domain Registration in Plasma Membrane Models". United States. https://doi.org/10.1021/acs.jpclett.8b01877. https://www.osti.gov/servlets/purl/1488792.
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@article{osti_1488792,
title = {Cholesterol Flip-Flop Impacts Domain Registration in Plasma Membrane Models},
author = {Thallmair, Sebastian and Ingólfsson, Helgi I. and Marrink, Siewert J.},
abstractNote = {The plasma membrane is a highly complex multicomponent system that is central to the functioning of cells. Cholesterol, a key lipid component of the plasma membrane, promotes the formation of nanodomains. These nanodomains are often correlated across the two membrane leaflets, but the underlying physical mechanism remains unclear. Using coarse-grained molecular dynamics simulations, we investigate the influence of cholesterol flip-flop on membrane properties, in particular, the interleaflet coupling of cholesterol-enriched domains. We show that the cholesterol density correlation between the leaflets of an average mammalian plasma membrane is significantly reduced by suppressing interleaflet cholesterol population. Our results suggest an amplifying role of cholesterol in signal transduction across the leaflets.},
doi = {10.1021/acs.jpclett.8b01877},
journal = {Journal of Physical Chemistry Letters},
number = 18,
volume = 9,
place = {United States},
year = {Fri Sep 07 00:00:00 EDT 2018},
month = {Fri Sep 07 00:00:00 EDT 2018}
}
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Journal Article:
Free Publicly Available Full Text
Publisher's Version of Record
https://doi.org/10.1021/acs.jpclett.8b01877
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Citation Metrics:
Cited by: 27 works
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Figures / Tables:

Figure 1. Figure 1.: Lipid mixtures of DPPC/DLiPC/CHOL (a/d), DPPC/DOPC/CHOL (b/e), and DPPC/DOPC/DLiPC/CHOL (c/f). a/b/c) Top and side view of the membrane organization after 30 µs of simulation without any restrictions on CHOL. DPPC is colored in blue; DOPC in purple; DLiPC in red; CHOL in yellow. The phospholipid headgroups are omittedmore » for clarity. d/e/f) Distributions of the Pearson correlation of the CHOL densities of the two leaflets evaluated for the last 20 µs of the simulations. Snapshots were taken every 500 ps without averaging.« less
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    Works referencing / citing this record:

    Recent Advances in Coarse-Grained Models for Biomolecules and Their Applications
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    Real-time cholesterol sorting in Plasmodium falciparum-erythrocytes as revealed by 3D label-free imaging
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