title: Interaction between amyloid-beta (1-42) peptide and phospholipid bilayers: a molecular dynamics study.
abstract: The amyloid-beta (Abeta) peptide is a key aggregate species in Alzheimer's disease. Although important aspects of Abeta peptide aggregation are understood, the initial stage of aggregation from monomer to oligomer is still not clear. One potential mediator of this early aggregation process is interactions of Abeta with anionic cell membranes. We used unconstrained and umbrella sampling molecular dynamics simulations to investigate interactions between the 42-amino acid Abeta peptide and model bilayers of zwitterionic dipalmitoylphosphatidylcholine (DPPC) lipids and anionic dioleoylphosphatidylserine (DOPS) lipids. Using these methods, we determined that Abeta is attracted to the surface of DPPC and DOPS bilayers over the small length scales used in these simulations. We also found supporting evidence that the charge on both the bilayer surface and the peptide affects the free energy of binding of the peptide to the bilayer surface and the distribution of the peptide on the bilayer surface. Our work demonstrates that interactions between the Abeta peptide and lipid bilayer promotes a peptide distribution on the bilayer surface that is prone to peptide-peptide interactions, which can influence the propensity of Abeta to aggregate into higher-order structures.
authors.affiliation: Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA. cdavis@email.unc.edu
authors.forename: Charles H
authors.initials: CH
authors.lastname: Davis
authors.forename: Max L
authors.initials: ML
authors.lastname: Berkowitz
mesh_terms: D015060:1,2-Dipalmitoylphosphatidylcholine / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000378:metabolism*; D055162:Biocatalysis; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism; D008051:Lipid Bilayers / Q000737:chemistry / Q000378:metabolism*; D008958:Models, Molecular; D019636:Neurodegenerative Diseases / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism*; D010718:Phosphatidylserines / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism*; D011485:Protein Binding; D017433:Protein Structure, Secondary; D015203:Reproducibility of Results; D013816:Thermodynamics
chemical_list: D016229:Amyloid beta-Peptides; D008051:Lipid Bilayers; D010446:Peptide Fragments; D010718:Phosphatidylserines; D010743:Phospholipids; C075222:amyloid beta-protein (1-42); D015060:1,2-Dipalmitoylphosphatidylcholine; C042511:1,2-dioleoylphosphatidylserine