Resonant Inhibition of polyQ Peptide Fibrillation via Vibrational Strong Coupling

Area of Science:

• Biophysics
• Molecular Biology
• Neurodegenerative Disease Research

Background:

• Amyloid fibril formation is central to neurodegenerative diseases like Huntington's.
• Current therapies for amyloid aggregation lack precision and can have side effects.
• Controlling peptide self-assembly at interfaces is crucial for understanding disease pathology.

Purpose of the Study:

• To introduce a noninvasive method to inhibit polyglutamine peptide fibrillation.
• To explore the use of vibrational strong coupling (VSC) for modulating protein misfolding.
• To investigate the mechanism of VSC-induced inhibition of amyloid aggregation.

Main Methods:

• Utilized optical microcavities to achieve vibrational strong coupling (VSC).
• Resonantly coupled water molecule vibrations to confined electromagnetic fields.
• Employed molecular dynamics simulations to understand the underlying mechanisms.
• Performed morphological analysis to quantify fibril formation.

Main Results:

• Achieved a 42.5% suppression of polyglutamine peptide fibrillation using VSC.
• Observed a 3-fold reduction in fibril density and significantly shorter fibril lengths.
• Disrupted the formation of the characteristic β-sheet network in amyloid fibrils.
• Molecular dynamics simulations indicated cavity-induced water rearrangement inhibits peptide nucleation.

Conclusions:

• Vibrational strong coupling (VSC) provides a precise and noninvasive method to inhibit amyloid aggregation.
• Solvent-vibration control is a novel strategy for modulating molecular self-assembly.
• This approach has potential applications in studying and treating protein misfolding diseases.