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Updated: Jun 3, 2025

Analysis of β-Amyloid-induced Abnormalities on Fibrin Clot Structure by Spectroscopy and Scanning Electron Microscopy
Published on: November 30, 2018
Amyloid beta (Aβ) fibrillation kinetics and its impact on membrane polarity
Arun Ajaikumar1, Nozomi Morishita Watanabe1, Keishi Suga2
1Division of Chemical Engineering, Graduate School of Engineering Science, Osaka University, 1-3 Machikaneyamacho, Toyonaka, Osaka, 560-8531, Japan.
Abstract:
Fibrillation of the amyloid beta (Aβ) peptide has often been associated with neurodegenerative pathologies such as Alzheimer's disease. In this study we examined the influence of several potential compositions of the lipid membrane on Aβ fibrillation by using liposomes as a basic model membrane. Firstly, it was revealed that Aβ fibrillation kinetics were enhanced and had the potential to occur at a faster rate on more fluid membranes compared to solid membranes. Next, the extent of fibril-related damage to membranes was examined with analysis of membrane polarity via the steady-state emission spectra of 6-dodecanoyl-2-dimethylaminonaphthalene (Laurdan). It was revealed that there was slight hydration behavior of the membrane during the lag phase (tlag) of the kinetic process, possibly coinciding with Aβ monomer binding. However, as the fibrillation kinetic process continued the membrane gradually dehydrated. Hydration states of membranes during and after Aβ fibrillation processes were further examined via deconvolution analysis of the obtained Laurdan spectra. This allows a mapping of membrane hydration from the interior to exterior regions of the lipid membrane. Results revealed slight but definitive variations in deeper region membrane polarity during the time course of Aβ fibrillation, suggesting Aβ aggregation impacts not only the surface level aggregating region but also the inner regions of the membrane. These results can ultimately contribute to the future investigations of the nature of the membrane damage caused by Aβ aggregation.
Insights
Amyloid beta (Aβ) peptide fibrillation accelerates on fluid lipid membranes, causing dehydration and impacting deeper membrane regions. This research offers insights into Aβ-induced membrane damage relevant to Alzheimer's disease.
Area of Science:
- Biochemistry
- Neuroscience
- Materials Science
Background:
- Amyloid beta (Aβ) peptide fibrillation is linked to neurodegenerative diseases like Alzheimer's.
- Lipid membranes play a crucial role in modulating Aβ aggregation and its pathological effects.
Purpose of the Study:
- To investigate how different lipid membrane compositions influence Aβ fibrillation kinetics and membrane damage.
- To analyze the impact of Aβ aggregation on membrane hydration and polarity.
Main Methods:
- Utilized liposomes as a model lipid membrane system.
- Monitored Aβ fibrillation kinetics.
- Analyzed membrane polarity and hydration using Laurdan fluorescence spectroscopy and deconvolution analysis.
Main Results:
- Aβ fibrillation kinetics were faster on more fluid membranes compared to solid membranes.
- Membrane dehydration occurred as fibrillation progressed.
- Aβ aggregation induced subtle but significant changes in deeper membrane regions' polarity.
Conclusions:
- Membrane fluidity significantly affects Aβ fibrillation rates.
- Aβ aggregation alters membrane hydration and polarity, affecting both surface and interior regions.
- Findings contribute to understanding Aβ-induced membrane damage in neurodegeneration.
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