Cholesterol Flip-Flop Impacts Domain Registration in Plasma Membrane Models

doi:10.1021/acs.jpclett.8b01877

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:

^[1];

^[2]; Marrink, Siewert J. ^[1]

Univ. of Groningen, Groningen (Netherlands). Groningen Biomolecular Sciences and Biotechnology Inst. and The Zernike Inst. for Advanced Material
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:: 2018-09-07

Research Org.:: Lawrence Livermore National Lab. (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) (SC-22)

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.  doi: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.  doi: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         = {2018},

  month        = {9}

}

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DOI: 10.1021/acs.jpclett.8b01877

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Figures / Tables:

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 »

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