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ToF-SIMS analysis of amyloid beta aggregation on different lipid membranes
Yuta Yokoyama1, Satoka Aoyagi1, Toshinori Shimanouchi2
1Department of Materials and Life Science, Seikei University, 3-3-1, Kichijyoji-kitamachi, Musashino, Tokyo 180-8633, Japan.
Abstract:
Amyloid beta (Aβ) peptides are considered to be strongly related to Alzheimer's disease. Aβ peptides form a β-sheet structure on hard lipid membranes and it would aggregate to form amyloid fibrils, which are toxic to cells. However, the aggregation mechanism of Aβ is not fully understood. To evaluate the influence of the lipid membrane condition for Aβ aggregation, the adsorption forms of Aβ (1-40) on mixture membranes of lipid 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) and cholesterol β-d-glucoside (β-CG) were investigated by time-of-flight secondary ion mass spectrometry. As a result, Aβ adsorbed along the localized DMPC lipid on the mixture lipid membranes, whereas it was adsorbed homogeneously on the pure DMPC and β-CG membranes. Moreover, amino acid fragments that mainly existed in the n-terminal of Aβ (1-40) peptide were strongly detected on the localized DMPC region. These results suggested that the Aβ was adsorbed along the localized DMPC lipid with a characteristic orientation. These findings suggest that the hardness of the membrane is very sensitive to coexisting materials and that surface hardness is important for aggregation of Aβ.
Insights
Amyloid beta (Aβ) aggregation on lipid membranes is influenced by membrane composition. Aβ peptides preferentially adsorb to specific lipid regions, suggesting membrane hardness is crucial for Alzheimer's disease-related fibril formation.
Area of Science:
- Biochemistry
- Neuroscience
- Materials Science
Background:
- Amyloid beta (Aβ) peptides are strongly implicated in Alzheimer's disease pathogenesis.
- Aβ aggregation into toxic amyloid fibrils involves formation of β-sheet structures on lipid membranes, but the mechanism remains unclear.
- Lipid membrane properties significantly influence protein aggregation.
Purpose of the Study:
- To investigate how lipid membrane composition affects Aβ (1-40) adsorption and aggregation.
- To evaluate the role of membrane hardness and heterogeneity in Aβ aggregation.
Main Methods:
- Time-of-flight secondary ion mass spectrometry (ToF-SIMS) was used to analyze Aβ (1-40) adsorption.
- Mixture membranes of 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) and cholesterol β-d-glucoside (β-CG) were employed.
- Comparison of Aβ adsorption on pure DMPC, pure β-CG, and mixed lipid membranes.
Main Results:
- Aβ (1-40) adsorbed non-homogeneously, specifically along localized DMPC regions on mixed lipid membranes.
- In contrast, Aβ (1-40) showed homogeneous adsorption on pure DMPC and β-CG membranes.
- Amino acid fragments from the N-terminal of Aβ (1-40) were predominantly detected in the localized DMPC regions, indicating specific orientation.
Conclusions:
- Aβ (1-40) adsorption is sensitive to lipid membrane heterogeneity and localized lipid domains.
- The findings highlight that membrane surface hardness, influenced by coexisting lipids, plays a critical role in Aβ aggregation.
- This provides insights into the initial steps of amyloid fibril formation relevant to Alzheimer's disease.
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