Gangliosides Destabilize Lipid Phase Separation in Multicomponent Membranes

Yang Liu, Jonathan Barnoud, Siewert J. Marrink*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

2 Citations (Scopus)

Abstract

Gangliosides (GMs) form an important class of lipids found in the outer leaflet of the plasma membrane. Typically, they colocalize with cholesterol and sphingomyelin in ordered membrane domains. However, detailed understanding of the lateral organization of GM-rich membranes is still lacking. To gain molecular insight, we performed molecular dynamics simulations of GMs in model membranes composed of coexisting liquid-ordered and liquid-disordered domains. We found that GMs indeed have a preference to partition into the ordered domains. At higher concentrations (>10 mol %), we observed a destabilizing effect of GMs on the phase coexistence. Further simulations with modified GMs show that the structure of the GM headgroup affects the phase separation, whereas the nature of the tail determines the preferential location. Together, our findings provide a molecular basis to understand the lateral organization of GM-rich membranes.

Original languageEnglish
Pages (from-to)1215-1223
Number of pages19
JournalBiophysical Journal
Volume117
Issue number7
Early online date6-Sep-2019
DOIs
Publication statusPublished - 1-Oct-2019

Keywords

  • MARTINI FORCE-FIELD
  • GM1 GANGLIOSIDE
  • COMPUTATIONAL LIPIDOMICS
  • PROTEIN INTERACTIONS
  • FUNCTIONAL RAFTS
  • DOMAIN FORMATION
  • CROSS-LINKING
  • MODEL
  • DYNAMICS
  • ORGANIZATION

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