Tuning the surface charge of phospholipid bilayers inhibits insulin fibrilization.

Tuning the surface charge of phospholipid bilayers inhibits insulin fibrilization.
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DOI:
10.1016/j.colsurfb.2022.112904
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发表时间:
2022-12
期刊:
Colloids and surfaces. B, Biointerfaces
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The interactions between proteins and materials, in particular lipid bilayers, has been studied extensively for their relevance in diseases and for the formulation of protein-based therapeutics and vaccines. However, the precise rules by which material properties induce favorable or unfavorable structural states in biomolecules are incompletely understood, and as a result, the rational design of materials remains challenging. Here, we investigated the influence of lipid bilayers (in the form of small unilamellar vesicles) on the formation of insulin amyloid fibrils using a fibril-specific assay (thioflavin T), polyacrylamide gel electrophoresis, and circular dichroism spectroscopy. Lipid bilayers composed of equal mixtures of cationic and anionic lipids effectively inhibited fibril formation and stabilized insulin in its native conformation. However, other lipid bilayer compositions failed to inhibit fibril formation or even destabilized insulin, exacerbating fibrilization and/or non-amyloid aggregation. Our findings suggest that electrostatic interactions with lipid bilayers can play a critical role in stabilizing or destabilizing insulin, and preventing the conversion of insulin to its amyloidogenic, disease-associated state.
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