Aggregation and partitioning of amyloid peptide fragments in the presence of a lipid bilayer: A coarse grained molecular dynamics study

Amyloidogenicity and toxicity of amyloid peptides have been linked to the peptide aggregation and interactions with lipid bilayers. In this work we used the coarse grained MARTINI model to study the aggregation and partitioning of amyloid peptide fragments A/3(1-28) and A/3(25-35) in the presence of a dipalmitoylphosphatidylcholine bilayer. We explored the peptide aggregation starting from three initial spatial arrangements where free monomers were placed in solution outside the membrane, at the membrane-solution interface, or in the membrane. We found that A/3(1-28) and A/3(25-35) interact with the bilayer quite differently. The A/3(1-28) fragments show strong peptide-peptide and peptide-lipid interactions leading to irreversible aggregation where the aggregates stay confined to their initial spatial location. The A/3(25-35) fragments show weaker peptidepeptide and peptide-lipid interaction leading to reversible aggregation and accumulation at the membranesolution interface irrespective of their initial spatial arrangement. Those findings can be explained in terms of the shape of the potential of mean force for the single-peptide translocation across the membrane.

Automated summary

The amyloidogenicity and toxicity of amyloid peptides are influenced by their aggregation and interactions with lipid bilayers. The study using MARTINI model found that A/3(1-28) fragments form irreversible aggregates with strong peptide-peptide and peptide-lipid interactions. On the other hand, A/3(25-35) fragments form reversible aggregates with weaker interactions and accumulate at the membrane-solution interface irrespective of their initial spatial arrangement.