Slow Dissolution Kinetics of Model Peptide Fibrils

Area of Science:

• Biochemistry
• Physical Chemistry
• Neuroscience

Background:

• Peptide self-assembly into amyloid fibrils is linked to neurodegenerative diseases.
• Understanding the kinetics of these processes is crucial for disease mechanism insights.

Purpose of the Study:

• To investigate the dissolution kinetics of self-assembled model peptide fibrils.
• To elucidate the rate-limiting steps in peptide fibril dissolution.

Main Methods:

• Utilized isothermal titration calorimetry (ITC) due to low peptide concentrations.
• Performed dilution quench experiments to initiate fibril dissolution.
• Conducted complementary pH experiments to study self-assembly mechanisms.

Main Results:

• Peptide fibril dissolution was observed to be a slow, reaction-limited process.
• Dissolution kinetics could be distinguished from rapid dilution-associated events in ITC.
• Self-assembly was found to involve partial deprotonation of peptide molecules.

Conclusions:

• The rate-limiting step in dissolution involves breaking inter-peptide beta-sheet hydrogen bonds.
• Formation of peptide-water hydrogen bonds is key in the dissolution process.
• Partial deprotonation during self-assembly influences fibril formation.