Phase networks of cross-β peptide assemblies

Area of Science:

• Biochemistry
• Biophysics
• Materials Science

Background:

• Simple peptides can form diverse amphiphilic phases.
• These structures are implicated in nearly 40 protein misfolding diseases.
• Amyloid assemblies are prevalent in neurodegenerative conditions.

Purpose of the Study:

• To map the morphologically accessible phases of the Aβ peptide.
• To understand the transitions between different peptide assembly states.
• To identify conditions that control amyloid formation.

Main Methods:

• Utilized a minimal nucleating core of the Aβ peptide.
• Employed fluorescence lifetime imaging microscopy (FLIM).
• Conducted transmission electron microscopy (TEM).

Main Results:

• Identified stable phases: molten particles, fibers, ribbons, and nanotubes.
• Observed liquid-liquid phase separations critical for transitions.
• Found size dependence for para-crystalline phase transition.
• Determined width of cross-β assemblies dictates fiber-ribbon transition.

Conclusions:

• Peptide assemblies form an interconnected network of increasing molecular order.
• Molten particles are critical for transitions to ordered cross-β peptide phases.
• Experimental findings extend initial computational models of cross-β assemblies.