title: Lipid composition influences the release of Alzheimer's amyloid β-peptide from membranes.
abstract: The behavior of the amyloid β-peptide (Aβ) within a membrane environment is integral to its toxicity and the progression of Alzheimer's disease. Ganglioside GM1 has been shown to enhance the aggregation of Aβ, but the underlying mechanism is unknown. Using atomistic molecular dynamics simulations, we explored the interactions between the 40-residue alloform of Aβ (Aβ(40) ) and several model membranes, including pure palmitoyloleoylphosphatidylcholine (POPC) and palmitoyloleoylphosphatidylserine (POPS), an equimolar mixture of POPC and palmitoyloleoylphosphatidylethanolamine (POPE), and lipid rafts, both with and without GM1, to understand the behavior of Aβ(40) in various membrane microenvironments. Aβ(40) remained inserted in POPC, POPS, POPC/POPE, and raft membranes, but in several instances exited the raft containing GM1. Aβ(40) interacted with GM1 largely through hydrogen bonding, producing configurations containing β-strands with C-termini that, in some cases, exited the membrane and became exposed to solvent. These observations provide insight into the release of Aβ from the membrane, a previously uncharacterized process of the Aβ aggregation pathway.
authors.affiliation: Department of Biochemistry, Virginia Tech, Blacksburg, Virginia 24061, USA.
authors.forename: Justin A
authors.initials: JA
authors.lastname: Lemkul
authors.forename: David R
authors.initials: DR
authors.lastname: Bevan
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000737:chemistry*; D005677:G(M1) Ganglioside / Q000737:chemistry; D006860:Hydrogen Bonding; D008567:Membranes, Artificial; D056004:Molecular Dynamics Simulation; D010713:Phosphatidylcholines / Q000737:chemistry; D010714:Phosphatidylethanolamines / Q000737:chemistry; D010718:Phosphatidylserines / Q000737:chemistry
chemical_list: D016229:Amyloid beta-Peptides; D008567:Membranes, Artificial; D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; D010718:Phosphatidylserines; D005677:G(M1) Ganglioside; C483858:phosphatidylethanolamine; C028694:1-palmitoyl-2-oleoylphosphatidylcholine