| AVS 65th International Symposium & Exhibition | |
| Biomaterial Interfaces Division | Tuesday Sessions |
| Session BI-TuP |
| Session: | Biomaterial Interfaces Division Poster Session |
| Presenter: | Eun Ji Shin, Pohang University of Science and Technology, Republic of Korea |
| Authors: | E.J. Shin, Pohang University of Science and Technology, Republic of Korea J.W. Park, Pohang University of Science and Technology, Republic of Korea |
| Correspondent: | Click to Email |
Alzheimer’s Disease (AD) and Parkinson’s Disease (PD) are neurodegenerative diseases resulting in progressive degeneration or death of neuron cells. These are associated with the aggregation of peptides, ‘amyloid-beta (Aβ)’ and ‘alpha-synuclein (α-syn)’. It is believed that Aβ and α-syn oligomers are intermediates in the fibril formation, and both oligomers and fibrils are primarily responsible for the pathogenesis. Further study showed that rate of the oligomerization (or aggregation) increases when Aβ and α-syn co-exist, and the co-existence causes the diseases even worse. It is very likely that hetero-oligomers could be formed, but presence and structure of the hetero-oligomers have not been elucidated.
Herein, we employed atomic force spectroscopy with a liquid cell to characterize the hetero-oligomers generated in vitro. For comparison, homo-oligomers were prepared separately. In particular, antibodies recognizing N-terminal of Aβ and N-terminal of α-syn were conjugated at AFM probes, and the specific interaction between the antibodies and surface of the oligomers was followed. After adsorbing the oligomers on mica surface, a tip tethering Aβ antibody was used to get high resolution force maps of a target oligomer, and subsequently another tip tethering α-syn antibody was brought to the same target for the examination. The overlaid map revealed that specific unbinding events with respect to two different antibodies were observed within an oligomer, and it holds for all sizes under investigation. Because homo-oligomers were not observed at all, it can be said that formation of hetero-oligomers is strongly favored. It is intriguing to note that the percentage of recognizing pixels for α-syn increases in comparison with the α-syn homo-oligomer, suggesting a different mode of aggregation for the hetero-oligomerization. We believe that such structural information helps to understand the relationship between the misfolded proteins and the pathogenesis in brain.