Fibril Fragmentation Enhances Amyloid Cytotoxicity*♦
| Autor: | Sheena E. Radford, Walraj S. Gosal, Andrew L. Hellewell, Eric W. Hewitt, Wei-Feng Xue, Steve W. Homans |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2009 |
| Předmět: |
Amyloid
Cell Survival Tetrazolium Salts macromolecular substances 010402 general chemistry Fibril Microscopy Atomic Force 01 natural sciences Biochemistry Models Biological 03 medical and health sciences Amyloid disease Mice Spectroscopy Fourier Transform Infrared medicine Animals Humans QD Viability assay Benzothiazoles Fragmentation (cell biology) Cytotoxicity Molecular Biology QC 030304 developmental biology 0303 health sciences Chemistry Amyloidosis Cell Biology medicine.disease 0104 chemical sciences Crystallography Kinetics Thiazoles Membrane Protein Structure and Folding Liposomes Biophysics QP517 Chickens HeLa Cells |
| Zdroj: | The Journal of Biological Chemistry |
| ISSN: | 1083-351X 0021-9258 |
| Popis: | Fibrils associated with amyloid disease are molecular assemblies of key biological importance, yet how cells respond to the presence of amyloid remains unclear. Cellular responses may not only depend on the chemical composition or molecular properties of the amyloid fibrils, but their physical attributes such as length, width, or surface area may also play important roles. Here, we report a systematic investigation of the effect of fragmentation on the structural and biological properties of amyloid fibrils. In addition to the expected relationship between fragmentation and the ability to seed, we show a striking finding that fibril length correlates with the ability to disrupt membranes and to reduce cell viability. Thus, despite otherwise unchanged molecular architecture, shorter fibrillar samples show enhanced cytotoxic potential than their longer counterparts. The results highlight the importance of fibril length in amyloid disease, with fragmentation not only providing a mechanism by which fibril load can be rapidly increased but also creating fibrillar species of different dimensions that can endow new or enhanced biological properties such as amyloid cytotoxicity. |
| Databáze: | OpenAIRE |
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