Related Experiment Video

Updated: May 29, 2025

Assembly of Cell Mimicking Supported and Suspended Lipid Bilayer Models for the Study of Molecular Interactions
12:18

Assembly of Cell Mimicking Supported and Suspended Lipid Bilayer Models for the Study of Molecular Interactions

Published on: August 3, 2021

3.4K

Depth-Resolved Temperature-Dependent Penetration of Polymyxin B in Phospholipids/Lipopolysaccharide Asymmetric

Nicoló Paracini1, Jeremy H Lakey2, Luke A Clifton3

  • 1Institut Laue-Langevin, Large Scale Structures Group, 71 Avenue des Martyrs, Grenoble 38000, France.

ACS Omega
|February 3, 2025
PubMed

Insights

Polymyxin B (PmB) antibiotic penetrates Gram-negative bacteria outer membranes by targeting lipopolysaccharides (LPS). This study reveals PmB accumulates in the lipid A hydrophobic region, hijacking LPS for entry.

Area of Science:

  • Microbiology
  • Biophysics
  • Structural Biology

Background:

  • Gram-negative bacteria possess a protective outer membrane (OM) with an asymmetric lipid bilayer.
  • Lipopolysaccharides (LPS) form the outer layer of the OM, acting as a barrier against harmful molecules.
  • Polymyxin B (PmB) is a critical antibiotic that disrupts the OM barrier by interacting with LPS.

Purpose of the Study:

  • To investigate the temperature-dependent penetration of PmB into fully deuterated OM models.
  • To quantify PmB penetration and localization within the asymmetric OM bilayer.
  • To elucidate the mechanism by which PmB interacts with LPS and lipid A.

Main Methods:

  • Utilized neutron reflectometry with fully deuterated OM models (2H-phospholipids and 2H-LPS).
  • Employed model-independent and model-dependent analyses to quantify PmB penetration and localization.
  • Leveraged neutron scattering's ability to differentiate hydrogen and deuterium.

Main Results:

  • PmB penetration into the OM model was quantified as a function of concentration and temperature.
  • Neutron reflectometry revealed PmB accumulates predominantly in the hydrophobic region of lipid A.
  • The study confirmed PmB hijacks LPS molecules for entry into the bacterial outer membrane.

Conclusions:

  • Polymyxin B targets the lipid A component of LPS within the bacterial outer membrane.
  • Understanding PmB-LPS interactions is crucial for developing new strategies against Gram-negative infections.
  • Neutron reflectometry provides a powerful tool for studying antibiotic-membrane interactions at a molecular level.

More Related Videos

Author Spotlight: Advancing Cell Membrane Biophysics - Exploring Interactions and Challenges Through Experimental and Computational Approaches07:31

Author Spotlight: Advancing Cell Membrane Biophysics - Exploring Interactions and Challenges Through Experimental and Computational Approaches

Published on: September 1, 2023

2.1K
Neutron Spin Echo Spectroscopy as a Unique Probe for Lipid Membrane Dynamics and Membrane-Protein Interactions10:02

Neutron Spin Echo Spectroscopy as a Unique Probe for Lipid Membrane Dynamics and Membrane-Protein Interactions

Published on: May 27, 2021

3.9K

Related Concept Videos

Asymmetric Lipid Bilayer01:35

Asymmetric Lipid Bilayer

Biological membranes show uneven distribution of different types of lipids in the inner and outer layers, resulting in transverse asymmetric membranes. The treatment of the erythrocyte membrane with the enzyme phospholipase confirmed the asymmetric nature of the lipid bilayer. The enzyme hydrolyzes lipids into fatty acids and hydrophilic groups. The phospholipase acts only on the outer layer of the membrane, while the inner layer remains intact. The phospholipase treatment resulted in 80%...
7.2K
Factors Affecting Dissolution: Drug pKa, Lipophilicity and GI pH01:21

Factors Affecting Dissolution: Drug pKa, Lipophilicity and GI pH

Drug absorption within the gastrointestinal (GI) tract is a complex process influenced by several critical factors, including the site pH, the drug's dissociation constant (pKa), and the drug's lipophilicity. The GI tract exhibits a pH gradient, with an acidic environment in the stomach and a more alkaline environment in the small intestine. This pH variation directly affects the ionization state of drugs.
A drug's pKa and the pH of the gastrointestinal (GI) tract play crucial roles...
998
Protein Diffusion in the Membrane01:24

Protein Diffusion in the Membrane

Proteins show rotational as well as lateral diffusion across the membrane. The lateral diffusion of proteins was confirmed through the cell fusion experiment where mouse and human cells were fused, resulting in hybrid cells. When the human and mouse cells fused, the specific membrane proteins on human and mouse cells were marked with the red and green-fluorescent markers, respectively. Initially, the red and green fluorescence was located on the respective hemisphere of the cell. As time...
4.3K
Membrane Fluidity01:23

Membrane Fluidity

Cell membranes are composed of phospholipids, proteins, and carbohydrates loosely attached to one another through chemical interactions. Molecules are generally able to move about in the plane of the membrane, giving the membrane its flexible nature called fluidity. Two other features of the membrane contribute to membrane fluidity: the chemical structure of the phospholipids and the presence of cholesterol in the membrane.
150.9K