Membrane curvature enhances lipid peroxidation in a composition-dependent manner

Area of Science:

• Biochemistry and Biophysics
• Cellular Biology
• Membrane Biophysics

Background:

• Excessive reactive oxygen species (ROS) cause oxidative stress, leading to lipid peroxidation in cellular membranes.
• Lipid peroxidation is implicated in various diseases and cell death pathways like ferroptosis.
• Understanding lipid peroxidation is challenging due to complex membrane compositions and morphologies.

Purpose of the Study:

• To quantify lipid oxidation as a function of both lipid composition and membrane curvature.
• To investigate the mechanisms by which membrane curvature and composition influence lipid peroxidation.
• To provide insights into how cells regulate or resist oxidative stress.

Main Methods:

• Utilized reconstituted lipid membranes and the fluorescent oxidation probe C11-BODIPY.
• Tethered synthetic lipid vesicles to glass substrates for per-vesicle monitoring.
• Employed fluorescence microscopy to quantify lipid oxidation rates and extents.

Main Results:

• Highly curved membranes significantly increase the rate and extent of lipid peroxidation across various compositions.
• Increased membrane curvature enhances ROS access to the hydrophobic core, promoting oxidation.
• Cholesterol's effect on oxidation is concentration-dependent, modulating curvature sensitivity.

Conclusions:

• Membrane curvature and lipid composition are interdependent factors determining oxidative susceptibility.
• Curved membranes are more vulnerable to lipid peroxidation, with implications for cellular health.
• Findings offer new insights into membrane stability and regulation of oxidative stress.