Multi-length scale structural investigation of lysozyme self-assembly

Area of Science:

• Biochemistry
• Biophysics
• Materials Science

Background:

• Reactive amyloid oligomers are cytotoxic and challenging to study due to their instability.
• Protein self-assembly in crowded environments is complex and crucial for cellular functions and pharmaceutical development.

Purpose of the Study:

• To investigate amyloid oligomerization in self-crowded lysozyme solutions under acidic conditions.
• To elucidate the formation and interconnection of amyloid oligomers and their impact on system properties.

Main Methods:

• Multi-length scale spectroscopic investigations.
• Analysis of thermal history and hierarchical self-assembly.

Main Results:

• Amyloid oligomers form at high protein concentration and low pH.
• Oligomers interconnect via weak, non-specific interactions, forming an extended network leading to system percolation.
• Hierarchical self-assembly significantly impacts functional properties.

Conclusions:

• Amyloid oligomer network formation is a critical aspect of amyloid pathologies.
• Understanding these self-assembly dynamics offers insights into cellular processes and pharmaceutical optimization.