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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...

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Detalles Bibliográficos
Autores principales: Ingólfsson, Helgi I., Carpenter, Timothy S., Bhatia, Harsh, Bremer, Peer-Timo, Marrink, Siewert J., Lightstone, Felice C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Biophysical Society 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5700369/
https://www.ncbi.nlm.nih.gov/pubmed/29113676
http://dx.doi.org/10.1016/j.bpj.2017.10.017
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author Ingólfsson, Helgi I.
Carpenter, Timothy S.
Bhatia, Harsh
Bremer, Peer-Timo
Marrink, Siewert J.
Lightstone, Felice C.
author_facet Ingólfsson, Helgi I.
Carpenter, Timothy S.
Bhatia, Harsh
Bremer, Peer-Timo
Marrink, Siewert J.
Lightstone, Felice C.
author_sort Ingólfsson, Helgi I.
collection PubMed
description 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. Here, 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.
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spelling pubmed-57003692018-11-21 Computational Lipidomics of the Neuronal Plasma Membrane Ingólfsson, Helgi I. Carpenter, Timothy S. Bhatia, Harsh Bremer, Peer-Timo Marrink, Siewert J. Lightstone, Felice C. Biophys J Articles 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. Here, 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. The Biophysical Society 2017-11-21 2017-11-04 /pmc/articles/PMC5700369/ /pubmed/29113676 http://dx.doi.org/10.1016/j.bpj.2017.10.017 Text en © 2017 Biophysical Society. http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Articles
Ingólfsson, Helgi I.
Carpenter, Timothy S.
Bhatia, Harsh
Bremer, Peer-Timo
Marrink, Siewert J.
Lightstone, Felice C.
Computational Lipidomics of the Neuronal Plasma Membrane
title Computational Lipidomics of the Neuronal Plasma Membrane
title_full Computational Lipidomics of the Neuronal Plasma Membrane
title_fullStr Computational Lipidomics of the Neuronal Plasma Membrane
title_full_unstemmed Computational Lipidomics of the Neuronal Plasma Membrane
title_short Computational Lipidomics of the Neuronal Plasma Membrane
title_sort computational lipidomics of the neuronal plasma membrane
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5700369/
https://www.ncbi.nlm.nih.gov/pubmed/29113676
http://dx.doi.org/10.1016/j.bpj.2017.10.017
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