Membrane curvature enhances oxidation within lipid bilayers in a composition-dependent manner

Area of Science:

• Biochemistry
• Cell Biology
• Materials Science

Background:

• Oxidative stress from excessive reactive oxygen species (ROS) production damages cellular membranes via lipid oxidation.
• Lipid oxidation is implicated in various diseases and can lead to cell death pathways like ferroptosis.
• Investigating lipid oxidation mechanisms is complex due to diverse membrane compositions and morphologies.

Purpose of the Study:

• To quantify oxidative responses in reconstituted lipid membranes.
• To investigate the influence of both lipid composition and membrane curvature on lipid oxidation.
• To understand the interplay between membrane structure and oxidative susceptibility.

Main Methods:

• Utilized reconstituted lipid bilayers and the fluorescent probe C11-BODIPY to measure oxidation.
• Employed fluorescence microscopy to monitor C11-BODIPY oxidation on tethered synthetic lipid vesicles.
• Systematically varied lipid composition and membrane curvature (vesicle size) to assess oxidative responses.

Main Results:

• Highly curved membranes significantly increased the rate and extent of C11-BODIPY oxidation across various lipid compositions.
• Compositional effects on oxidation were most prominent in low-curvature membranes and diminished with increasing curvature.
• Cholesterol was found to suppress oxidation in unsaturated phosphatidylcholine membranes, irrespective of curvature.

Conclusions:

• Membrane curvature and lipid composition are interdependent factors determining oxidative susceptibility.
• Increased membrane curvature enhances lipid tail exposure, facilitating ROS-associated chemistry.
• Findings provide insights into oxidative stress in simplified lipid systems and potential disease mechanisms.