Electrostatics controls the formation of amyloid superstructures in protein aggregation

Area of Science:

• Biophysics
• Materials Science
• Computational Biology

Background:

• Protein aggregation into diverse superstructures (large-scale polymorphism) is frequently observed.
• The underlying physicochemical mechanisms driving these aggregations remain poorly understood.

Purpose of the Study:

• To develop a theoretical model explaining the formation of generic protein aggregates.
• To elucidate the role of electrostatic interactions in protein aggregate morphology and growth.

Main Methods:

• Development of a theoretical model for charged protein aggregates.
• Analysis of multifractal structures and growth geometry.
• Comparison of model predictions with experimental aggregate growth curves.

Main Results:

• The model predicts multifractal aggregate structures.
• Electrostatic interactions between proteins dictate aggregate geometry and growth.
• Model predictions align with experimental data for aggregate growth.

Conclusions:

• A theoretical framework connecting protein interactions, aggregate morphology, and growth kinetics has been established.
• The model successfully explains complex protein aggregate formation in both in vivo and in vitro conditions.
• This work provides insights into the mechanisms of protein self-assembly.