# Fatty Acids Reverse the Supramolecular Chirality of Insulin Fibrils

## TL;DR

Fatty acids change the structure of insulin fibrils, reversing their chirality through hydrophobic interactions.

## Contribution

This study reveals how fatty acids reverse supramolecular chirality in insulin fibrils through molecular interactions.

## Key findings

- LCUFAs and LCPUFAs reverse the supramolecular chirality of insulin fibrils.
- Molecular dynamics simulations show strong hydrophobic interactions between fatty acids and insulin residues.
- Insulin:FA complexes have different self-assembly mechanisms compared to insulin alone.

## Abstract

Long-chain unsaturated and polyunsaturated fatty acids
(LCUFAs
and LCPUFAs, respectively) are the essential components of phospholipids
and sphingolipids, major building blocks of plasma and organelle membranes.
These molecules are also involved in cell signaling and energy metabolism.
Hence, both LCUFAs and LCPUFAs are broadly used as food supplements.
However, the role of these fatty acids (FAs) in the self-assembly
of misfolded proteins remains unclear. In this study, we investigated
the effect of LCUFAs and LCPUFAs, as well as their saturated analogue,
on insulin aggregation. Using vibrational circular dichroism, we found
that all analyzed FAs reversed the supramolecular chirality of insulin
fibrils. Molecular dynamics simulations showed that strong hydrophobic
interactions were formed between the long aliphatic tails of FAs and
hydrophobic amino acid residues of insulin. We infer that such insulin:FA
complexes had different self-assembly mechanisms compared to that
of insulin alone, which resulted in the observed reversal of the supramolecular
chirality of the amyloid fibrils.