Abstract
The interaction between lipid bilayers and Amyloid β peptide (Aβ) plays a critical role in proliferation of Alzheimer’s disease (AD). AD is expected to affect one in every 85 humans by 2050, and therefore, deciphering the interplay of Aβ and lipid bilayers at the molecular level is of profound importance. In this work, we applied an array of neutron scattering methods to study the structure and dynamics of Aβ(1–40) interacting 1,2-dimyristoyl-sn-glycero-3-phosphoglycerol (DMPG) bilayers. In the structural investigations of lipid bilayer’s response to Aβ binding, Small Angle Neutron Scattering and Neutron Membrane Diffraction revealed that the Aβ anchors firmly to the highly charged DMPG bilayers in the interfacial region between water and hydrocarbon chain, and it doesn’t penetrate deeply into the bilayer. This association mode is substantiated by the dynamics studies with high resolution Quasi-Elastic Neutron Scattering experiments, showing that the addition of Aβ mainly affects the slower lateral motion of lipid molecules, especially in the fluid phase, but not the faster internal motion. The results revealed that Aβ associates with the highly charged membrane in surface with limited impact on the structure, but the altered membrane dynamics could have more influence on other membrane processes.
Highlights
Amyloid βpeptide (Aβ) is the constituent of the amyloid fibril plaques found in Alzheimer’s disease patients
We demonstrated that the neutron techniques, including Small Angle Neutron Scattering (SANS), Neutron Membrane Diffraction (NMD), and Quasi-Elastic Neutron Scattering (QENS), for the first time to our knowledge, reveal the underlying molecular interactions between Aβand model membrane systems composed of a negatively charged lipid, 1,2-dimyristoyl-sn-glycero-3-phosphoglycerol (DMPG)
The “surface binding” nature of the interaction induced by charged lipid could enable Aβto assemble into oligomers or aggregate on the extended surface provided by cell membranes
Summary
Amyloid βpeptide (Aβ) is the constituent of the amyloid fibril plaques found in Alzheimer’s disease patients. Two model membrane systems were used: unilamellar vesicle (ULV) in solution provides a system close to physiologically relevant condition to observe the lipid bilayer change and Aβtransformation by SANS and QENS, while the substrate-supported multilamellar bilayer provides a more ordered system to resolve details of Aβin bilayers by NMD.
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