Binding of amyloid-like peptides to lipid bilayers: effects of ions and lipid content

In amyloid diseases, cell toxicity can emerge from interactions of peptides with the cell membrane. Several factors have been shown to modulate the magnitude of these peptide-bilayer interactions, which can enhance or inhibit cell toxicity. These factors include lipid composition, the presence of ions in the solution. Here, we perform all-atom molecular dynamics simulations to provide an understanding at the atomic level of peptide-bilayer interactions and their modulation by Ca²⁺ and selected lipids. We find that both electrostatic and hydrophobic interactions contribute to peptide-bilayer binding. In particular, the binding is induced by positively charged residues interacting with lipid head groups. Hydrophobic interaction sustains this bound state. These mechanisms in detail as well as how they are affected by Ca²⁺ and selected lipid content of the bilayer will be discussed in detail. Additionally, we investigate the sequence dependence of peptide-bilayer interactions, showing that several factors such as net charge, sequence pattern and type of positive residues, can significantly affect the binding strength.