Tuning the surface charge of phospholipid bilayers inhibits insulin fibrilization

• Published in: Colloids and surfaces, B, Biointerfaces Vol. 220; p. 112904
• Main Authors: Reichelderfer, Victoria T., Chaparro Sosa, Andres F., Kaar, Joel L., Schwartz, Daniel K.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.12.2022
• Subjects: Aggregation; Amyloid; Amyloid - metabolism; Catanionic lipids; Insulin; Lipid bilayers; Lipid Bilayers - chemistry; Phospholipids - chemistry; Protein misfolding; Catanionic lipids; Aggregation; Amyloid; Protein misfolding; Insulin; Lipid bilayers
• ISSN: 0927-7765; 1873-4367
• DOI: 10.1016/j.colsurfb.2022.112904

The interactions between proteins and materials, in particular lipid bilayers, have 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. [Display omitted] •Phospholipid bilayers can impact the stability of amyloidgenic proteins.•Catanionic vesicles inhibit insulin aggregation and unfolding.•Stabilization of insulin was dependent on vesicle surface charge.•Understanding can be used to fine tune interactions of insulin with lipid bilayers.