Protein Polymerization into Fibrils from the Viewpoint of Nucleation Theory

Area of Science:

• Biophysics
• Materials Science
• Biochemistry

Background:

• Protein fibril assembly is crucial in biological systems and nanotechnology.
• The Oosawa-Kasai (OK) model describes protein polymerization into fibrils.
• Understanding the kinetics of fibril formation is essential for controlling aggregation.

Purpose of the Study:

• To analyze protein polymerization into linear and helical fibrils using nucleation theory.
• To investigate nucleation-mediated polymerization within a modified Oosawa-Kasai (OK) model.
• To derive key kinetic parameters for fibril formation.

Main Methods:

• Application of general kinetic results from nucleation theory.
• Analysis of protein polymerization within the Oosawa-Kasai (OK) model framework.
• Derivation of expressions for fibril nucleus size, nucleation barrier, and size distributions.

Main Results:

• Modified OK model demonstrates nucleation-mediated linear protein polymerization.
• Expressions for fibril nucleus size, work for formation, and nucleation barrier were derived.
• Stationary fibril nucleation rate depends on monomer concentration and monomer loss rates of sub- and supernucleus fibrils.

Conclusions:

• Protein fibril formation can be nucleation-mediated, contrary to the original OK model for linear polymerization.
• The derived nucleation rate dependence offers experimental verification pathways.
• The findings are applicable to both linear and helical protein fibrils.