Polyphenol-Mediated Modulation of Amyloid-Lipid Interactions

Abstract

Förster resonance energy transfer (FRET) between the membrane fluorescent probes pyrene and TDV was employed to investigate the modulation of amyloid-lipid interactions by polyphenols. The effects of various polyphenols, including quercetin, curcumin, gallic and salicylic acids, on the complexation between the amyloid fibrils derived from N-terminal fragment of apolipoprotein A-I (ApoA-IF) and insulin (InsF), and liposomes composed of phosphatidylcholine (PC) and its mixtures with cardiolipin (CL), cholesterol (Chol), or phosphatidylglycerol (PG) were investigated. The incorporation of polyphenols resulted in decreased energy transfer efficiency, indicating a significant alteration in the spatial relationship between amyloid fibrils and lipid membranes. The magnitude of this effect was found to be dependent on lipid bilayer composition, the chemical nature of the polyphenols, and the type of amyloidogenic protein. Notably, curcumin exhibited the most pronounced impact across all systems, with a particularly strong effect on ApoA-IF compared to InsF. This differential response suggests protein-specific mechanisms of interaction and highlights the potential for targeted therapeutic approaches. Our findings provide novel insights into the intricate interplay between polyphenols, amyloid fibrils, and lipid membranes, contributing to the fundamental understanding of amyloid-related pathologies and opening new avenues for the development of polyphenol-based therapeutic strategies in amyloid-associated disorders.

Keywords

• Amyloid fibrils
• Lipid bilayer
• Polyphenols
• Förster resonance energy transfer