Computational Lipidomics of the Neuronal Plasma Membrane

Helgi I. Ingólfsson, Timothy S. Carpenter, Harsh Bhatia, Peer Timo Bremer, Siewert J. Marrink, Felice C Lightstone

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2271-2280
Number of pages10
JournalBiophysical Journal
Volume113
Issue number10
DOIs
StatePublished - Nov 21 2017
Externally publishedYes

Fingerprint

Cell Membrane
Lipids
Membrane Lipids
Brain
Membranes
Molecular Dynamics Simulation
Organelles
Tail
Homeostasis
Cholesterol
Diet

ASJC Scopus subject areas

  • Biophysics

Cite this

Ingólfsson, H. I., Carpenter, T. S., Bhatia, H., Bremer, P. T., Marrink, S. J., & Lightstone, F. C. (2017). Computational Lipidomics of the Neuronal Plasma Membrane. Biophysical Journal, 113(10), 2271-2280. https://doi.org/10.1016/j.bpj.2017.10.017

Computational Lipidomics of the Neuronal Plasma Membrane. / Ingólfsson, Helgi I.; Carpenter, Timothy S.; Bhatia, Harsh; Bremer, Peer Timo; Marrink, Siewert J.; Lightstone, Felice C.

In: Biophysical Journal, Vol. 113, No. 10, 21.11.2017, p. 2271-2280.

Research output: Contribution to journalArticle

Ingólfsson, HI, Carpenter, TS, Bhatia, H, Bremer, PT, Marrink, SJ & Lightstone, FC 2017, 'Computational Lipidomics of the Neuronal Plasma Membrane', Biophysical Journal, vol. 113, no. 10, pp. 2271-2280. https://doi.org/10.1016/j.bpj.2017.10.017
Ingólfsson HI, Carpenter TS, Bhatia H, Bremer PT, Marrink SJ, Lightstone FC. Computational Lipidomics of the Neuronal Plasma Membrane. Biophysical Journal. 2017 Nov 21;113(10):2271-2280. https://doi.org/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. In: Biophysical Journal. 2017 ; Vol. 113, No. 10. pp. 2271-2280.
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