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Polarization-Sensitive Two-Photon Microscopy for a Label-Free Amyloid Structural Characterization
Published on: September 8, 2023
Conformational memory effect reverses chirality of vortex-induced insulin amyloid superstructures
Wojciech Dzwolak1, Weronika Surmacz-Chwedoruk, Viktoria Babenko
1Department of Chemistry, University of Warsaw, Pasteura 1, 02-093 Warsaw, Poland. wdzwolak@chem.uw.edu.pl
Langmuir : the ACS Journal of Surfaces and Colloids
|December 14, 2012
Summary
Amyloid fibrils formed from insulin exhibit memory effects, influencing their structure and properties. Cross-seeding with different insulin variants alters the resulting amyloid superstructure, demonstrating how subtle changes impact global characteristics.
Area of Science:
- Biophysics
- Materials Science
- Biochemistry
Background:
- Amyloid fibril formation is a complex process often occurring far from equilibrium.
- Insulin serves as a model polypeptide for studying amyloidogenesis and its associated phenomena.
- Amyloid fibrils exhibit self-propagation through seeding, leading to distinct structural variants.
Purpose of the Study:
- To investigate the role of conformational memory effects in insulin fibril formation.
- To explore cross-seeding interactions between bovine insulin ([BI]) and Lys(B31)-Arg(B32) human insulin analogue ([KR]) fibrils.
- To understand how subtle conformational changes in fibrils influence macroscopic properties.
Main Methods:
- Infrared absorption spectroscopy to analyze fibril structure.
- Thioflavin T binding assays to detect chiral properties via extrinsic Cotton effect.
- Controlled agitation and cross-seeding experiments with bovine insulin and [KR] insulin analogue.
Main Results:
- Bovine insulin ([BI]) fibrils and [KR] insulin analogue fibrils were shown to cross-seed each other.
- [BI] fibrils formed chiral superstructures with a negative extrinsic Cotton effect in the absence of [KR] seeds.
- Cross-seeding [BI] with [KR] seeds resulted in daughter fibrils with a positive extrinsic Cotton effect.
Conclusions:
- Conformational memory effects in insulin fibrils encode distinct structural features in daughter fibrils.
- Subtle variations in single fibril conformation (e.g., β-strand alignment and twist) can lead to significant changes in global amyloid superstructure properties.
- Cross-seeding is a critical factor in determining the emergent properties of insulin amyloid fibrils.
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