Aggregation of Aß(25-35) on DOPC and DOPC/DHA bilayers: an atomic force microscopy study

Matilde Sublimi Saponetti; Manuela Grimaldi; Mario Scrima; Cristiano Albonetti; Stefania Lucia Nori; Annamaria Cucolo; Fabrizio Bobba; Anna Maria D'Ursi

doi:10.1371/journal.pone.0115780

Aggregation of Aß(25-35) on DOPC and DOPC/DHA bilayers: an atomic force microscopy study

PLoS One. 2014 Dec 31;9(12):e115780. doi: 10.1371/journal.pone.0115780. eCollection 2014.

Authors

Matilde Sublimi Saponetti¹, Manuela Grimaldi², Mario Scrima², Cristiano Albonetti³, Stefania Lucia Nori⁴, Annamaria Cucolo⁵, Fabrizio Bobba⁵, Anna Maria D'Ursi²

Affiliations

¹ Physics Department and Research Centre for Nanomaterials and Nanotechnology, University of Salerno, Via Giovanni Paolo II, 132, 84084, Fisciano (SA), Italy.
² Department of Pharmacy, University of Salerno, Via Giovanni Paolo II, 132, 84084, Fisciano (SA), Italy.
³ Institute for Superconductivity and Innovative Materials of the Italian National Research Council, Via Giovanni Paolo II, 132, 84084, Fisciano (SA), Italy; Institute Study Nanostructurated Materials of the Italian National Research Council, Via P. Gobetti 101, 40129, Bologna, Italy.
⁴ Department of Medicine and Surgery, University of Salerno, Via Salvatore Allende, 84081, Baronissi (SA), Italy.
⁵ Physics Department and Research Centre for Nanomaterials and Nanotechnology, University of Salerno, Via Giovanni Paolo II, 132, 84084, Fisciano (SA), Italy; Institute for Superconductivity and Innovative Materials of the Italian National Research Council, Via Giovanni Paolo II, 132, 84084, Fisciano (SA), Italy.

Abstract

β amyloid peptide plays an important role in both the manifestation and progression of Alzheimer disease. It has a tendency to aggregate, forming low-molecular weight soluble oligomers, higher-molecular weight protofibrillar oligomers and insoluble fibrils. The relative importance of these single oligomeric-polymeric species, in relation to the morbidity of the disease, is currently being debated. Here we present an Atomic Force Microscopy (AFM) study of Aβ(25-35) aggregation on hydrophobic dioleoylphosphatidylcholine (DOPC) and DOPC/docosahexaenoic 22∶6 acid (DHA) lipid bilayers. Aβ(25-35) is the smallest fragment retaining the biological activity of the full-length peptide, whereas DOPC and DOPC/DHA lipid bilayers were selected as models of cell-membrane environments characterized by different fluidity. Our results provide evidence that in hydrophobic DOPC and DOPC/DHA lipid bilayers, Aβ(25-35) forms layered aggregates composed of mainly annular structures. The mutual interaction between annular structures and lipid surfaces end-results into a membrane solubilization. The presence of DHA as a membrane-fluidizing agent is essential to protect the membrane from damage caused by interactions with peptide aggregates; to reduces the bilayer defects where the delipidation process starts.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Alzheimer Disease / pathology
Amyloid beta-Peptides / chemistry*
Cell Membrane / metabolism
Docosahexaenoic Acids / chemistry*
Humans
Hydrophobic and Hydrophilic Interactions
Lipid Bilayers / chemistry*
Microscopy, Atomic Force*
Phosphatidylcholines / chemistry*
Plaque, Amyloid / chemistry

Substances

Amyloid beta-Peptides
Lipid Bilayers
Phosphatidylcholines
Docosahexaenoic Acids
1,2-oleoylphosphatidylcholine

Grants and funding

This work was supported by fund of the University of Salerno ORSA131088. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.