title: Dual Effect of (LK)nL Peptides on the Onset of Insulin Amyloid Fiber Formation at Hydrophobic Surfaces.
abstract: 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.
authors.forename: Karim
authors.initials: K
authors.lastname: Chouchane
authors.affiliation: ‡Cergy Pontoise University, ERRMECe, I-MAT FD4122, F-95302 Cergy Pontoise, France.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Vendrely
authors.forename: Myriam
authors.initials: M
authors.lastname: Amari
authors.forename: Katie
authors.initials: K
authors.lastname: Moreaux
authors.forename: Franz
authors.initials: F
authors.lastname: Bruckert
authors.forename: Marianne
authors.initials: M
authors.lastname: Weidenhaupt
mesh_terms: D000327:Adsorption; D000595:Amino Acid Sequence; D000682:Amyloid / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D005456:Fluorescent Dyes / Q000737:chemistry; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D007328:Insulin / Q000737:chemistry*; D007700:Kinetics; D008958:Models, Molecular; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology*; D066329:Protein Aggregates; D055503:Protein Multimerization / Q000187:drug effects*; D017433:Protein Structure, Secondary; D013499:Surface Properties
chemical_list: D000682:Amyloid; D005456:Fluorescent Dyes; D007328:Insulin; D010446:Peptide Fragments; D066329:Protein Aggregates