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Accelerated insulin aggregation under alternating current electric fields: Relevance to amyloid kinetics
Zhongli Zheng1, Benxin Jing1, Mirco Sorci2
1Department of Chemical and Biomolecular Engineering, University of Notre Dame , Notre Dame, Indiana 46556, USA.
Biomicrofluidics
|September 5, 2015
Summary
Applying AC electric fields accelerates insulin amyloid fibrillation, shortening lag times from months to hours. This controlled nucleation offers insights into protein aggregation and related diseases.
Area of Science:
- Biophysics
- Biochemistry
- Materials Science
Background:
- Amyloid fibrillation is critical to pathologies, with nucleation and oligomer formation as key mechanisms.
- Understanding the time-dependent nucleation phase is crucial for disease research.
Purpose of the Study:
- To investigate the control and examination of insulin aggregation using non-uniform AC electric fields.
- To explore the impact of AC fields on amyloid nucleation kinetics.
Main Methods:
- Utilized AC-electroosmosis flow for insulin concentration under AC fields.
- Employed fluorescence correlation spectroscopy and fluorescence microscopy for analysis.
- Maintained a constant temperature of 20°C in aqueous buffer solution.
Main Results:
- Insulin rapidly concentrated in AC fields (0.5-2 kHz) via AC-electroosmosis.
- Observed direct fibrillation from insulin monomers, bypassing oligomer precursors.
- Significantly shortened aggregation lag time from months/years to 1-3 hours.
Conclusions:
- External AC electric fields can effectively control and accelerate amyloid nucleation.
- Altering nucleation kinetics with electric fields provides insights into amyloid disease mechanisms.
- Demonstrated a novel method for studying and potentially modulating protein aggregation.
