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09:44
Generation of Alpha-Synuclein Preformed Fibrils from Monomers and Use In Vivo
Published on: June 2, 2019
Watching amyloid fibrils grow by time-lapse atomic force microscopy
C Goldsbury1, J Kistler, U Aebi
1School of Biological Sciences, University of Auckland, New Zealand.
Journal of Molecular Biology
|January 8, 1999
Summary
Late-onset diabetes involves amylin fibrils. Time-lapse atomic force microscopy revealed human amylin fibril growth dynamics, showing bidirectional elongation at 1.1 nm/minute, offering new insights into amyloid formation.
Area of Science:
- Biochemistry
- Biophysics
- Cell Biology
Background:
- Late-onset diabetes is linked to fibrillar amylin deposits in pancreatic islets.
- Human amylin forms polymorphic fibrils in vitro, a process relevant to disease pathogenesis.
Purpose of the Study:
- To investigate the dynamics of human amylin fibril assembly in vitro.
- To characterize the growth kinetics and morphology of individual amylin fibrils.
Main Methods:
- Utilized time-lapse atomic force microscopy (AFM) to observe individual amylin fibril growth on a mica surface over several hours.
- Monitored fibril elongation rates, directionality, and morphological changes at the single-molecule level.
Main Results:
- Observed the assembly of protofibrils with a measured elongation rate of 1.1 nm/minute.
- Demonstrated bidirectional growth of protofibrils, occurring at both ends.
- Documented the formation of higher-order polymorphic fibrils.
Conclusions:
- Time-lapse AFM provides a powerful method to study fibril dynamics, overcoming limitations of bulk spectroscopy methods.
- The observed fibril assembly dynamics offer insights into the mechanisms of amylin aggregation in diabetes.
- This AFM approach is potentially applicable to studying fibril formation in other amyloidogenic proteins and peptides.
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