Amyloid aggregation on lipid bilayers and its impact on membrane permeability

Area of Science:

• Biophysics
• Molecular Biology
• Pathology

Background:

• Fibrillar protein aggregates, known as amyloids, are implicated in diseases like Alzheimer's and type II diabetes.
• Cell membrane disruption and leakage by amyloid aggregates are believed to cause toxicity, but the mechanism remains unclear.

Purpose of the Study:

• To investigate the molecular mechanism of membrane damage caused by fibril-forming peptides.
• To elucidate the role of peptide aggregation in lipid bilayer disruption and cellular leakage.

Main Methods:

• Coarse-grained molecular dynamics simulations.
• Modeling fibril-forming amphipathic peptides interacting with lipid vesicles.

Main Results:

• Highly amyloidogenic peptides fibrillate on vesicle surfaces, leading to bilayer damage and leakage.
• Vesicles hinder the ordered aggregation of peptides with low amyloidogenicity.
• Growing amyloid aggregates, not mature fibrils, induce vesicle leakage.

Conclusions:

• Peptide aggregation on cell membranes can cause bilayer disruption and leakage, contributing to amyloid-related pathologies.
• The stage of aggregate growth (growing vs. mature) is critical in determining membrane damage.
• Simulation findings provide a molecular basis for experimental observations of fibril-forming polypeptide behavior.