Molecular Rotors Provide Insights into Microscopic Structural Changes During Protein Aggregation.

Area of Science:

• Soft matter physics
• Biophysics
• Materials science

Background:

• Protein aggregation into amyloid fibrils is linked to neurodegenerative diseases.
• Understanding the microrheology of protein aggregation is crucial for disease mechanism studies.
• Microscopic viscosity changes are key indicators of structural transitions in soft matter.

Purpose of the Study:

• To investigate microrheological changes during protein-to-amyloid fibril gel transition.
• To apply molecular rotors as probes for protein aggregation dynamics.
• To explore mechanistic stages of protein aggregation using advanced fluorescence techniques.

Main Methods:

• Utilizing molecular rotors to monitor changes in microscopic viscosity.
• Employing phasor analysis of fluorescence decay signals.
• Comparing molecular rotor data with classical fluorescent probes.

Main Results:

• Observed an increase in system rigidity by approximately three orders of magnitude during aggregation.
• Phasor analysis indicated multiple distinct mechanistic stages in the aggregation process.
• Demonstrated molecular rotors' ability to detect microrheological features missed by traditional probes.

Conclusions:

• Molecular rotors are effective tools for studying protein aggregation and gelation.
• The study provides new insights into the microrheological landscape of amyloid fibril formation.
• This approach enhances the understanding of protein structural transitions relevant to neurodegenerative disorders.