Interactions of lipopolysaccharide with lipid membranes, raft models - A solid state NMR study

Filip Ciesielski, David C. Griffin, Michael Rittig, Ignacio Moriyón, Boyan B. Bonev

Research output: Journal PublicationArticlepeer-review

18 Citations (Scopus)

Abstract

Lipopolysaccharide (LPS) is a major component of the external leaflet of bacterial outer membranes, key pro-inflammatory factor and an important mediator of host-pathogen interactions. In host cells it activates the complement along with a pro-inflammatory response via a TLR4-mediated signalling cascade and shows preference for cholesterol-containing membranes. Here, we use solid state 13C and 31P MAS NMR to investigate the interactions of LPS from three bacterial species, Brucella melitensis, Klebsiella pneumoniae and Escherichia coli, with mixed lipid membranes, raft models. All endotoxin types are found to be pyrophosphorylated and Klebsiellar LPS is phosphonylated, as well. Carbon-13 MAS NMR indicates an increase in lipid order in the presence of LPS. Longitudinal 31P relaxation, providing a direct probe of LPS molecular and segmental mobility, reveals a significant reduction in 31P T1 times and lower molecular mobility in the presence of ternary lipid mixtures. Along with the ordering effect on membrane lipid, this suggests a preferential partitioning of LPS into ordered bilayer sphingomyelin/cholesterol-rich domains. We hypothesise that this is an important evolutionary drive for the selection of GPI-anchored raft-associated LPS-binding proteins as a first line of response to membrane-associated LPS.

Original languageEnglish
Pages (from-to)1731-1742
Number of pages12
JournalBiochimica et Biophysica Acta - Biomembranes
Volume1828
Issue number8
DOIs
Publication statusPublished - 2013
Externally publishedYes

Keywords

  • Endotoxin
  • High resolution solid state NMR
  • Host-pathogen interactions
  • Lipid domains
  • Longitudinal relaxation
  • LPS

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Cell Biology

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