Self-assembly of protein amyloids: a competition between amorphous and ordered aggregation

Area of Science:

• Biochemistry
• Biophysics
• Materials Science

Background:

• Protein aggregation into amyloid fibrils is biologically significant and technologically relevant.
• Thermodynamic equilibrium of protein aggregation systems should account for both fibrillar and disordered aggregates.
• Disordered aggregates, such as micelles, can coexist with amyloid fibrils.

Purpose of the Study:

• To model the thermal equilibrium of protein aggregation considering monomeric proteins, disordered aggregates (micelles), and fibrillar aggregates (amyloid fibrils).
• To investigate the influence of disordered species on the thermodynamic behavior of protein aggregation.
• To enhance the understanding of empirical amyloid-promoting factors and fibrillization kinetics.

Main Methods:

• Development of a model based on binding free energies for monomeric proteins, micelles, and amyloid fibrils.
• Calculation of the concentrations of these species at thermal equilibrium.
• Analysis of how incorporating disordered structures impacts the understanding of aggregation phenomena.

Main Results:

• The study calculates equilibrium concentrations for different protein aggregation states.
• It demonstrates the importance of including disordered aggregates in thermodynamic models.
• Findings provide insights into factors influencing amyloid formation.

Conclusions:

• Accounting for disordered protein aggregates, like micelles, is crucial for a complete thermodynamic description of amyloid fibril formation.
• This approach improves the understanding of empirically observed amyloid-promoting factors.
• The model offers a framework for further investigation into the kinetics of protein fibrillization.