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Title: Computational Lipidomics of the Neuronal Plasma Membrane

Membrane lipid composition varies greatly within submembrane compartments, different organelle membranes, and also between cells of different cell stage, cell and tissue types, and organisms. Environmental factors (such as diet) also influence membrane composition. The membrane lipid composition is tightly regulated by the cell, maintaining a homeostasis that, if disrupted, can impair cell function and lead to disease. This is especially pronounced in the brain, where defects in lipid regulation are linked to various neurological diseases. The tightly regulated diversity raises questions on how complex changes in composition affect overall bilayer properties, dynamics, and lipid organization of cellular membranes. We utilize recent advances in computational power and molecular dynamics force fields to develop and test a realistically complex human brain plasma membrane (PM) lipid model and extend previous work on an idealized, “average” mammalian PM. The PMs showed both striking similarities, despite significantly different lipid composition, and interesting differences. The main differences in composition (higher cholesterol concentration and increased tail unsaturation in brain PM) appear to have opposite, yet complementary, influences on many bilayer properties. Both mixtures exhibit a range of dynamic lipid lateral inhomogeneities (“domains”). The domains can be small and transient or larger and more persistent and canmore » correlate between the leaflets depending on lipid mixture, Brain or Average, as well as on the extent of bilayer undulations.« less
Authors:
 [1] ;  [1] ;  [2] ;  [2] ;  [3] ;  [1]
  1. Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States). Biosciences and Biotechnology Division and Physical and Life Sciences Directorate
  2. Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States). Center for Applied Scientific Computing (CASC) and Computational Directorate
  3. Univ. of Groningen (Netherlands). Groningen Biomolecular Science and Biotechnology Inst. and the Zernike Inst. for Advanced Materials
Publication Date:
Report Number(s):
LLNL-JRNL-733434
Journal ID: ISSN 0006-3495; 885101
Grant/Contract Number:
AC52-07NA27344; 16-FS-007; AC5206NA25396; AC05-00OR22725; HHSN261200800001E
Type:
Published Article
Journal Name:
Biophysical Journal
Additional Journal Information:
Journal Volume: 113; Journal Issue: 10; Journal ID: ISSN 0006-3495
Publisher:
Elsevier
Research Org:
Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Frederick National Lab. for Cancer Research (FNLCR), Frederick, MD (United States)
Sponsoring Org:
USDOE National Nuclear Security Administration (NNSA); USDOE Laboratory Directed Research and Development (LDRD) Program; National Institutes of Health (NIH)
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; 97 MATHEMATICS AND COMPUTING
OSTI Identifier:
1408151
Alternate Identifier(s):
OSTI ID: 1474388

Ingólfsson, Helgi I., Carpenter, Timothy S., Bhatia, Harsh, Bremer, Peer-Timo, Marrink, Siewert J., and Lightstone, Felice C.. Computational Lipidomics of the Neuronal Plasma Membrane. United States: N. p., Web. doi:10.1016/j.bpj.2017.10.017.
Ingólfsson, Helgi I., Carpenter, Timothy S., Bhatia, Harsh, Bremer, Peer-Timo, Marrink, Siewert J., & Lightstone, Felice C.. Computational Lipidomics of the Neuronal Plasma Membrane. United States. doi:10.1016/j.bpj.2017.10.017.
Ingólfsson, Helgi I., Carpenter, Timothy S., Bhatia, Harsh, Bremer, Peer-Timo, Marrink, Siewert J., and Lightstone, Felice C.. 2017. "Computational Lipidomics of the Neuronal Plasma Membrane". United States. doi:10.1016/j.bpj.2017.10.017.
@article{osti_1408151,
title = {Computational Lipidomics of the Neuronal Plasma Membrane},
author = {Ingólfsson, Helgi I. and Carpenter, Timothy S. and Bhatia, Harsh and Bremer, Peer-Timo and Marrink, Siewert J. and Lightstone, Felice C.},
abstractNote = {Membrane lipid composition varies greatly within submembrane compartments, different organelle membranes, and also between cells of different cell stage, cell and tissue types, and organisms. Environmental factors (such as diet) also influence membrane composition. The membrane lipid composition is tightly regulated by the cell, maintaining a homeostasis that, if disrupted, can impair cell function and lead to disease. This is especially pronounced in the brain, where defects in lipid regulation are linked to various neurological diseases. The tightly regulated diversity raises questions on how complex changes in composition affect overall bilayer properties, dynamics, and lipid organization of cellular membranes. We utilize recent advances in computational power and molecular dynamics force fields to develop and test a realistically complex human brain plasma membrane (PM) lipid model and extend previous work on an idealized, “average” mammalian PM. The PMs showed both striking similarities, despite significantly different lipid composition, and interesting differences. The main differences in composition (higher cholesterol concentration and increased tail unsaturation in brain PM) appear to have opposite, yet complementary, influences on many bilayer properties. Both mixtures exhibit a range of dynamic lipid lateral inhomogeneities (“domains”). The domains can be small and transient or larger and more persistent and can correlate between the leaflets depending on lipid mixture, Brain or Average, as well as on the extent of bilayer undulations.},
doi = {10.1016/j.bpj.2017.10.017},
journal = {Biophysical Journal},
number = 10,
volume = 113,
place = {United States},
year = {2017},
month = {11}
}