FRET studies of lipid-protein aggregates related to amyloid-like fibers.

Acidic lipids are known to both catalyze amyloid fiber formation by amyloidogenic peptides/proteins and induce formation of 'amyloid-like' fibrils by non-amyloidogenic proteins. In this work, we describe the application of state-of-the-art time-resolved Förster resonance energy transfer methodologies to the characterization of the supramolecular structure of the aggregates formed by both a cationic peptide (hexalysyltryptophan) and a basic non-amyloidogenic protein (lysozyme) upon their interaction with negatively-charged fluid membranes (mixtures of zwitterionic phosphatidylcholine and anionic phosphatidylserine). It was concluded that both the peptide and protein induce the formation of multistacked lipid bilayers. Furthermore, upon using conditions that are described in the literature to cause the formation of amyloid-like fibers, lysozyme was found to induce the formation of a 'pinched lamellar' structure, with reduced interbilayer distance in the regions where there is bound protein, and increased interbilayer distance (stabilized by hydration repulsion) outside these areas. No significant lateral domains (lipid demixing) were induced in the membrane by either the cationic peptide or lysozyme.