Open AccessTime-Dependent Lipid Dynamics, Organization and Peptide-Lipid Interaction in Phospholipid Bilayers with Incorporated β-Amyloid Oligomers
Author(s) -
Qiang Wang,
Katelynne E. Doherty,
Lukas M. Klees,
Yuto Tobin-Miyaji
Publication year - 2020
Publication title -
the journal of physical chemistry letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.563
H-Index - 203
ISSN - 1948-7185
DOI - 10.1021/acs.jpclett.0c01967
Subject(s) - oligomer , phospholipid , membrane , lipid bilayer , biophysics , chemistry , peptide , amyloid (mycology) , molecular dynamics , biological membrane , biochemistry , biology , organic chemistry , inorganic chemistry , computational chemistry
Nonfibrillar β-amyloid (Aβ) oligomers are considered as major neurotoxic species in the pathology of Alzheimer's disease. The presence of Aβ oligomers was shown to cause membrane disruptions in a broad range of model systems. However, the molecular basis of such a disruption process remains unknown. We previously demonstrated that membrane-incorporated 40-residue Aβ (Aβ 40 ) oligomers could form coaggregates with phospholipids. This process occurred more rapidly than the fibrillization of Aβ 40 and led to more severe membrane disruption. The present study probes the time-dependent changes in lipid dynamics, bilayer structures, and peptide-lipid interactions along the time course of the oligomer-induced membrane disruption, using solid-state NMR spectroscopy. Our results suggest the presence of certain intermediate states with phospholipid molecules entering the C-terminal hydrogen-bonding networks of the Aβ 40 oligomeric cores. This work provides insights on the molecular mechanisms of Aβ 40 -oligomer-induced membrane disruption.