Molecular mechanism of material-induced insulin aggregation.
type: Dataset
contact point: Organization
  fn: CCSD
keyword: conformational-changes
keyword: chaperones
keyword: changement-de-conformation
keyword: stabilite
keyword: stability
keyword: protein
keyword: chaperons
keyword: proteine
keyword: physcondcm-genphysics-physicscondensed-matter-cond-matother-cond-matother
keyword: surfaces
keyword: theses
keyword: infoeu-reposemanticsdoctoralthesis
keyword: agregation
landing page: https://theses.hal.science/tel-00846390
description: Material surface-induced protein aggregation is important for the stability of therapeutic proteins. Using human insulin, we first study its amyloidal aggregation on neutral hydrophobic or hydrophilic surfaces and show that nucleation takes place on the hydrophobic surfaces at both pH 2.5 and 7.3. We show that the activation energy for nucleation is lower on hydrophobic surfaces than in solution. We observed that agitating the solution has several antagonistic effects. In particular, the hydrodynamic shear stress detaches surface-borne fibrils. Using Surface Plasmon Resonance imaging, infrared spectroscopy and fluorescence microscopy we then define the sequence of molecular events that happen at the interface between hydrophobic materials and fluid phase. Insulin first adsorbs rapidly on the surface and then continues to accumulate, in parallel with an alpha-to beta-structural transition leading to amyloid fibril formation. Hereafter, we study the mechanism of action of a small peptide known to accelerate insulin aggregation (LVEALYL). This peptide stably adsorbs in β-conformation on the surface and helps accumulating insulin on the surface. Moreover, it appears that its sequence is not essential for its effectiveness, since several peptides, having a β-sheet structure on the surface, induce insulin aggregation. The presence of prolines abolishes its pro-aggregative activity. These results shed light on the molecular details of insulin self-association. The hydrophobic nature of material surfaces facilitates the unfolding of adsorbed insulin, resulting in the exposure of the LVEALYL peptide segment. This peptide promotes the propagation of conformational changes among incoming proteins. Counteracting this propagation could help stabilizing protein solutions.
identifier: NNT: 2012GRENY087
issued: 2026-05-10T07:08:33.117586
language: fr
modified: 2026-05-10T07:08:33.117590

test_moissonnage_selune
type: Agent

Molecular mechanism of material-induced insulin aggregation.
type: Distribution
access URL: https://theses.hal.science/tel-00846390
format: HTML
issued: 2026-05-10T07:08:33.135628
modified: 2026-05-10T07:08:33.104410