Membrane Determinants Affect Fibrillation Processes of β-Sheet Charged Peptides

Area of Science:

• Biochemistry
• Materials Science
• Neuroscience

Background:

• Peptide fibril assembly is influenced by intrinsic properties and external factors.
• Beta-sheet structures can form functional assemblies or toxic amyloid fibrils implicated in neurodegenerative diseases.
• Membrane bilayers are known initiators and modulators of amyloid fibrillation, but the mechanisms remain unclear.

Purpose of the Study:

• To investigate the impact of zwitterionic and negatively charged bilayer vesicles on the assembly structures of three charged peptides prone to beta-sheet fibril formation.
• To elucidate the relationship between peptide/membrane charges and fibrillation properties.

Main Methods:

• Utilized a set of three charged peptides with beta-sheet fibril forming tendencies.
• Employed microscopic and spectroscopic experiments to analyze peptide assembly structures in the presence of bilayer vesicles.
• Investigated the effects of zwitterionic and negatively charged vesicles on peptide fibrillation.

Main Results:

• Observed an intimate relationship between peptide/membrane charges and fibrillation properties.
• Electrostatic attraction between oppositely charged peptides and vesicles did not significantly alter fibril morphology for net anionic or cationic peptides.
• A zwitterionic peptide formed unique twisted fiber morphologies in the presence of negatively charged vesicles due to counterionic interactions.

Conclusions:

• Membrane charge and peptide charge significantly influence beta-sheet fibril assembly.
• Negatively charged vesicles can template unique fibril morphologies in zwitterionic peptides through charge-mediated interactions.
• These findings demonstrate the critical role of membrane-mediated interactions in modulating peptide fibril structures.