Distinct Membrane Disruption Pathways Are Induced by 40-Residue β-Amyloid Peptides*
| Autor: | Christof Grewer, Hyeongeun Kim, Wei Qiang, Qinghui Cheng, He Dong, Dawei Xu, Katelynne E. Doherty, Dennis A. Delgado |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Amyloid Vesicle fusion Magnetic Resonance Spectroscopy Membrane lipids Lipid Bilayers Plasma protein binding Biology 010402 general chemistry 01 natural sciences Biochemistry Protein Aggregation Pathological Ion Channels Cell membrane 03 medical and health sciences Membrane Lipids Alzheimer Disease medicine Humans Lipid bilayer Molecular Biology Ion channel Phospholipids Liposome Amyloid beta-Peptides Microscopy Confocal Circular Dichroism Cell Membrane Cell Biology Peptide Fragments 0104 chemical sciences 030104 developmental biology Membrane medicine.anatomical_structure Spectrometry Fluorescence Liposomes Biophysics Molecular Biophysics Protein Binding |
| Popis: | Cellular membrane disruption induced by β-amyloid (Aβ) peptides has been considered one of the major pathological mechanisms for Alzheimer disease. Mechanistic studies of the membrane disruption process at a high-resolution level, on the other hand, are hindered by the co-existence of multiple possible pathways, even in simplified model systems such as the phospholipid liposome. Therefore, separation of these pathways is crucial to achieve an in-depth understanding of the Aβ-induced membrane disruption process. This study, which utilized a combination of multiple biophysical techniques, shows that the peptide-to-lipid (P:L) molar ratio is an important factor that regulates the selection of dominant membrane disruption pathways in the presence of 40-residue Aβ peptides in liposomes. Three distinct pathways (fibrillation with membrane content leakage, vesicle fusion, and lipid uptake through a temporarily stable ionic channel) become dominant in model liposome systems under specific conditions. These individual systems are characterized by both the initial states of Aβ peptides and the P:L molar ratio. Our results demonstrated the possibility to generate simplified Aβ-membrane model systems with a homogeneous membrane disruption pathway, which will benefit high-resolution mechanistic studies in the future. Fundamentally, the possibility of pathway selection controlled by P:L suggests that the driving forces for Aβ aggregation and Aβ-membrane interactions may be similar at the molecular level. |
| Databáze: | OpenAIRE |
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