Amyloid Fibril Solubility

TL;DR

This study uses simulations to explore how interactions between amyloid fibril building blocks influence their solubility, revealing general rules that could aid in designing fibrils with specific properties.

Contribution

It introduces a simple protein model and analytical formula to relate fibril interactions with solubility, advancing understanding of amyloid fibril behavior.

Findings

Fibril solubility depends on fibril thickness.

Interaction strength influences solubility.

Temperature and side-chain interactions affect fibril stability.

Abstract

It is well established that amyloid fibril solubility is protein specific, but how solubility depends on the interactions between the fibril building blocks is not clear. Here we use a simple protein model and perform Monte Carlo simulations to directly measure the solubility of amyloid fibrils as a function of the interaction between the fibril building blocks. Our simulations confirms that the fibril solubility depends on the fibril thickness and that the relationship between the interactions and the solubility can be described by a simple analytical formula. The results presented in this study reveal general rules how side-chain side-chain interactions, backbone hydrogen bonding and temperature affect amyloid fibril solubility, which might prove a powerful tool to design protein fibrils with desired solubility and aggregation properties in general.