title: Probing the interplay between amyloidogenic proteins and membranes using lipid monolayers and bilayers.
abstract: Many degenerative diseases such as Alzheimer's and Parkinson's involve proteins that have a tendency to misfold and aggregate eventually forming amyloid fibers. This review describes the use of monolayers, bilayers, supported membranes, and vesicles as model systems that have helped elucidate the mechanisms and consequences of the interactions between amyloidogenic proteins and membranes. These are twofold: membranes favor the formation of amyloid structures and these induce damage in those membranes. We describe studies that show how interfaces, especially charged ones, favor amyloidogenic protein aggregation by several means. First, surfaces increase the effective protein concentration reducing a three-dimensional system to a two-dimensional one. Second, charged surfaces allow electrostatic interactions with the protein. Anionic lipids as well as rafts, rich in cholesterol and gangliosides, prove to play an especially important role. Finally, these amphipathic systems also offer a hydrophobic environment favoring conformational changes, oligomerization, and eventual formation of mature fibers. In addition, we examine several models for membrane permeabilization: protein pores, leakage induced by extraction of lipids, chaotic pores, and membrane tension, presenting illustrative examples of experimental evidence in support of these models. The picture that emerges from recent work is one where more than one mechanism is in play. Which mechanism prevails depends on the protein, its aggregation state, and the lipid environment in which the interactions occur.
authors.affiliation: Department of Physics, University of Genoa, Genoa, Italy; Research Centre on the Molecular Basis of Neurodegeneration, Florence, Italy.
authors.forename: Annalisa
authors.initials: A
authors.lastname: Relini
authors.affiliation: Department of Physics, University of Genoa, Genoa, Italy; Department of Chemistry, Saint Lawrence University, Canton, NY, United States.
authors.forename: Nadia
authors.initials: N
authors.lastname: Marano
authors.affiliation: Department of Physics, University of Genoa, Genoa, Italy. Electronic address: gliozzi@fisica.unige.it.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Gliozzi
mesh_terms: D058227:Amyloidogenic Proteins / Q000737:chemistry* / Q000378:metabolism; D000818:Animals; D055592:Biophysical Phenomena; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008051:Lipid Bilayers / Q000737:chemistry* / Q000378:metabolism; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism; D008954:Models, Biological; D066263:Protein Aggregation, Pathological / Q000378:metabolism; D013499:Surface Properties; D053835:Unilamellar Liposomes / Q000737:chemistry* / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D058227:Amyloidogenic Proteins; D008051:Lipid Bilayers; D008565:Membrane Proteins; D053835:Unilamellar Liposomes
keywords: Amyloid aggregation; Amyloid toxicity; Membrane model systems; Membrane permeabilization; Membrane-assisted fibrillogenesis