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dc.contributor.authorPoojari, Chetan
dc.contributor.authorKukol, A.
dc.contributor.authorStrodel, Birgit
dc.date.accessioned2013-08-07T08:48:17Z
dc.date.available2013-08-07T08:48:17Z
dc.date.issued2013-02
dc.identifier.citationPoojari , C , Kukol , A & Strodel , B 2013 , ' How the amyloid-β peptide and membranes affect each other : An extensive simulation study ' , Biochimica et Biophysica Acta - Biomembranes , vol. 1828 , no. 2 , 327-339 . https://doi.org/10.1016/j.bbamem.2012.09.001
dc.identifier.issn0006-3002
dc.identifier.otherPURE: 1186488
dc.identifier.otherPURE UUID: 256cfa2f-b8c1-4664-9920-8811d872090a
dc.identifier.otherPubMed: 22975281
dc.identifier.otherScopus: 84869868315
dc.identifier.urihttp://hdl.handle.net/2299/11322
dc.descriptionCopyright © 2012. Published by Elsevier B.V.
dc.description.abstractThe etiology of Alzheimer's disease is thought to be linked to interactions between amyloid-β (Aβ) and neural cell membranes, causing membrane disruption and increased ion conductance. The effects of Aβ on lipid behavior have been characterized experimentally, but structural and causal details are lacking. We used atomistic molecular dynamics simulations totaling over 6μs in simulation time to investigate the behavior of Aβ(42) in zwitterionic and anionic lipid bilayers. We simulated transmembrane β-sheets (monomer and tetramer) resulting from a global optimization study and a helical structure obtained from an NMR study. In all simulations Aβ(42) remained embedded in the bilayer. It was found that the surface charge and the lipid tail type are determinants for transmembrane stability of Aβ(42) with zwitterionic surfaces and unsaturated lipids promoting stability. From the considered structures, the β-sheet tetramer is most stable as a result of interpeptide interactions. We performed an in-depth analysis of the translocation of water in the Aβ(42)-bilayer systems. We observed that this process is generally fast (within a few nanoseconds) yet generally slower than in the peptide-free bilayers. It is mainly governed by the lipid type, simulation temperature and Aβ(42) conformation. The rate limiting step is the permeation through the hydrophobic core, where interactions between Aβ(42) and permeating H(2)Omolecules slow the translocation process. The β-sheet tetramer allows more water molecules to pass through the bilayer compared to monomeric Aβ, allowing us to conclude that the experimentally observed permeabilization of membranes must be due to membrane-bound Aβ oligomers, and not monomers.en
dc.language.isoeng
dc.relation.ispartofBiochimica et Biophysica Acta - Biomembranes
dc.titleHow the amyloid-β peptide and membranes affect each other : An extensive simulation studyen
dc.contributor.institutionHealth & Human Sciences Research Institute
dc.contributor.institutionSchool of Life and Medical Sciences
dc.contributor.institutionDepartment of Human and Environmental Sciences
dc.contributor.institutionAgriculture, Veterinary and Food Sciences
dc.contributor.institutionPharmacology and Clinical Science Research
dc.contributor.institutionCardiovascular Pathologies
dc.contributor.institutionBiochemistry and Bioinformatics
dc.contributor.institutionBiosciences Research Group
dc.description.statusPeer reviewed
rioxxterms.versionSMUR
rioxxterms.versionofrecordhttps://doi.org/10.1016/j.bbamem.2012.09.001
rioxxterms.typeJournal Article/Review
herts.preservation.rarelyaccessedtrue


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