ArticleLangmuir : the ACS journal of surfaces and colloids2015
Effect of divalent cation removal on the structure of gram-negative bacterial outer membrane models.
Article in Langmuir : the ACS journal of surfaces and colloids, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 168 papers.
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Who cites it
168 citing papers in PubMed, 370 citations in OpenAlex.
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- Marine Antimicrobial Peptide as a Promising Alternative to Polymyxin B.Marine drugs · 2026Article
- Influence of Lipomannan and Lipoarabinomannan Concentration on Mycobacterial Inner Membranes Characterized by All-atom Simulations.bioRxiv : the preprint server for biology · 2026Article
- Lipopolysaccharide confinement in the bacterial outer membrane is governed by interactions within the conserved Lipid A anchor.The EMBO journal · 2026Article
- Martini 3 as a Transferable Force Field for Lipopolysaccharide Parametrization.The journal of physical chemistry. B · 2026Article
- Broxyquinoline enhances antibacterial activity of colistin and attenuates LPS-induced inflammation.Antimicrobial agents and chemotherapy · 2026Article
- From Membrane Composition to Antimicrobial Strategies: Experimental and Computational Approaches to AMP Design and Selectivity.Small (Weinheim an der Bergstrasse, Germany) · 2026Review
- Bacterial cell envelope-targeting antibiotics.Nature reviews. Microbiology · 2026Review
- Antimicrobial Peptide Activity in Lipid Bilayers with Smooth-Type Lipopolysaccharides.Analytical chemistry · 2026Article
- Sequential electroporation and biomimetic mineralization on anRSC advances · 2026Article
108 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 5 institutions in 3 countries.
Funding
Abstract
The Gram-negative bacterial outer membrane (GNB-OM) is asymmetric in its lipid composition with a phospholipid-rich inner leaflet and an outer leaflet predominantly composed of lipopolysaccharides (LPS). LPS are polyanionic molecules, with numerous phosphate groups present in the lipid A and core oligosaccharide regions. The repulsive forces due to accumulation of the negative charges are screened and bridged by the divalent cations (Mg(2+) and Ca(2+)) that are known to be crucial for the integrity of the bacterial OM. Indeed, chelation of divalent cations is a well-established method to permeabilize Gram-negative bacteria such as Escherichia coli. Here, we use X-ray and neutron reflectivity (XRR and NR, respectively) techniques to examine the role of calcium ions in the stability of a model GNB-OM. Using XRR we show that Ca(2+) binds to the core region of the rough mutant LPS (RaLPS) films, producing more ordered structures in comparison to divalent cation free monolayers. Using recently developed solid-supported models of the GNB-OM, we study the effect of calcium removal on the asymmetry of DPPC:RaLPS bilayers. We show that without the charge screening effect of divalent cations, the LPS is forced to overcome the thermodynamically unfavorable energy barrier and flip across the hydrophobic bilayer to minimize the repulsive electrostatic forces, resulting in about 20% mixing of LPS and DPPC between the inner and outer bilayer leaflets. These results reveal for the first time the molecular details behind the well-known mechanism of outer membrane stabilization by divalent cations. This confirms the relevance of the asymmetric models for future studies of outer membrane stability and antibiotic penetration.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.