Lipid Chain Oxidation Promotes Binding of Acute-Phase C-Reactive Protein to Cell Membranes

Area of Science:

• Biochemistry
• Immunology
• Membrane Biophysics

Background:

• C-reactive protein (CRP) is a key inflammatory biomarker.
• CRP binds to oxidized phosphatidylcholine (PC) on apoptotic cells, initiating complement activation.
• CRP's interaction with PC membranes is dependent on oxidized PC (OxPC).

Purpose of the Study:

• To investigate how oxidized PC (OxPC) affects C-reactive protein (CRP)-membrane interactions.
• To elucidate the mechanism by which CRP binds to and modifies apoptotic cell membranes.

Main Methods:

• Incorporation of oxidized lipid products (aldehyde and carboxylate moieties) into PC vesicles.
• Monitoring CRP-vesicle interactions using dynamic light scattering.
• Analyzing membrane properties via Fourier analysis of membrane fluctuation.

Main Results:

• CRP induced fusion of OxPC-containing vesicles, with faster kinetics for carboxylated lipids.
• Non-oxidized PC vesicles remained intact upon CRP addition.
• CRP exhibited Ca²⁺-dependent higher affinity for OxPC vesicles, which were softer and thinner.
• CRP binding stiffened the OxPC-containing membranes.

Conclusions:

• Oxidized PC (OxPC) incorporation into membranes alters their biophysical properties, making them softer and thinner.
• CRP preferentially binds to OxPC-containing membranes in a Ca²⁺-dependent manner.
• CRP binding to OxPC-enriched, Ca²⁺-condensed membranes stiffens them, potentially contributing to apoptotic cell clearance.