Publication

Computational Lipidomics of the Neuronal Plasma Membrane

Ingólfsson, H. I., Carpenter, T. S., Bhatia, H., Bremer, P-T., Marrink, S. J. & Lightstone, F. C., 21-Nov-2017, In : Biophysical Journal. 113, 10, p. 2271-2280 10 p., j.bpj.2017.10.017.

Research output: Contribution to journalArticleAcademicpeer-review

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

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
Article numberj.bpj.2017.10.017
Pages (from-to)2271-2280
Number of pages10
JournalBiophysical Journal
Volume113
Issue number10
Early online date4-Nov-2017
Publication statusPublished - 21-Nov-2017

    Keywords

  • Computational lipidomics, Neural Plasma membrane, Molecular Dynamics simulation, Martini CG model, RAPID SEPARATION , PROTEIN FUNCTION, MOLECULAR-DYNAMICS SIMULATIONS, PERFORMANCE LIQUID-CHROMATOGRAPHY, LIGHT-SCATTERING DETECTION, FATTY-ACID-COMPOSITION, COARSE-GRAINED MODEL, MARTINI FORCE-FIELD, RAT-BRAIN, MASS-SPECTROMETRY

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