Dual Effect of (LK)nL Peptides on the Onset of Insulin Amyloid Fiber Formation at Hydrophobic Surfaces

Soluble proteins are constantly in contact with material or cellular surfaces, which can trigger their aggregation and therefore have a serious impact on the development of stable therapeutic proteins. In contact with hydrophobic material surfaces, human insulin aggregates readily into amyloid fiber...

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Bibliographic Details
Published in:The journal of physical chemistry. B 2015-08, Vol.119 (33), p.10543-10553
Main Authors: Chouchane, Karim, Vendrely, Charlotte, Amari, Myriam, Moreaux, Katie, Bruckert, Franz, Weidenhaupt, Marianne
Format: Article
Language:English
Subjects:
Adsorption
Agglomeration
Amino Acid Sequence
Amyloid - chemistry
Chemical Sciences
Contact
Dose-Response Relationship, Drug
Fluorescent Dyes - chemistry
Formations
Humans
Hydrophobic and Hydrophilic Interactions
Insulin
Insulin - chemistry
Kinetics
Material chemistry
Models, Molecular
Nuclei
Peptide Fragments - chemistry
Peptide Fragments - pharmacology
Peptides
Protein Aggregates
Protein Multimerization - drug effects
Protein Structure, Secondary
Proteins
Surface chemistry
Surface Properties
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Summary:Soluble proteins are constantly in contact with material or cellular surfaces, which can trigger their aggregation and therefore have a serious impact on the development of stable therapeutic proteins. In contact with hydrophobic material surfaces, human insulin aggregates readily into amyloid fibers. The kinetics of this aggregation can be accelerated by small peptides, forming stable beta-sheets on hydrophobic surfaces. Using a series of (LK)­nL peptides with varying length, we show that these peptides, at low, substoichiometric concentrations, have a positive, cooperative effect on insulin aggregation. This effect is based on a cooperative adsorption of (LK)­nL peptides at hydrophobic surfaces, where they form complexes that help the formation of aggregation nuclei. At higher concentrations, they interfere with the formation of an aggregative nucleus. These effects are strictly dependent on the their adsorption on hydrophobic material surfaces and highlight the importance of the impact of materials on protein stability. (LK)­nL peptides prove to be valuable tools to investigate the mechanism of HI aggregation nuclei formation on hydrophobic surfaces.
ISSN:1520-6106
1520-5207
DOI:10.1021/acs.jpcb.5b07365