Fluorescence study on aggregated lysozyme and lipid bilayer interactions

Area of Science:

• Biochemistry
• Biophysics
• Membrane Biology

Background:

• Lysozyme (Lz) is implicated in various amyloid-related conditions.
• Understanding the interaction of Lz aggregates with biological membranes is crucial.
• Lipid bilayers, composed of phosphatidylcholine/cardiolipin (PC/CL), are fundamental cellular structures.

Purpose of the Study:

• To investigate the impact of lysozyme (Lz) oligomers on the physicochemical properties of PC/CL membranes.
• To elucidate the mechanism of Lz oligomer binding to lipid bilayers.
• To compare the effects of different Lz aggregation states (monomers, oligomers, fibrils) on membrane integrity.

Main Methods:

• Utilized fluorescent probes: 1,6-diphenyl-1,3,5-hexatriene (DPH), pyrene, 4-dimethylaminochalcone (DMC), and 4-p-(dimethylaminostyryl)-1-dodecylpyridinium (DSP-12).
• Analyzed spectral responses of probes to detect changes in membrane properties.
• Investigated binding interactions between Lz oligomers and lipid bilayers.

Main Results:

• Incorporation of Lz self-assemblies led to reduced membrane free volume.
• A decrease in lipid bilayer surface hydration was observed.
• Hydrophobic interactions were identified as the primary driver for Lz oligomer binding.
• Soluble Lz oligomeric intermediates demonstrated the most detrimental effect on membrane properties compared to monomers and fibrils.

Conclusions:

• Lysozyme oligomers significantly alter the physicochemical properties of PC/CL membranes.
• The binding of Lz oligomers to membranes is mediated by hydrophobic interactions.
• Soluble Lz oligomers represent the most disruptive species to membrane integrity, highlighting their potential role in disease pathogenesis.