Electrostatics controls the formation of amyloid-like superstructures in protein aggregation

TL;DR

This paper introduces a theoretical model explaining how electrostatic interactions influence the formation and morphology of amyloid-like protein aggregates, successfully matching experimental observations and unifying physical mechanisms.

Contribution

It presents a novel, general theoretical framework linking electrostatics, aggregate morphology, and growth kinetics in protein aggregation.

Findings

Model predicts multi-fractal aggregate structures.

Experimental data confirms model accuracy.

Applicable to both in vivo and in vitro conditions.

Abstract

The possibility for proteins to aggregate in different superstructures, i.e. large-scale polymorphism, has been widely observed, but an understanding of the physico-chemical mechanisms behind it is still out of reach. Here we present a theoretical model for the description of a generic aggregate formed from an ensemble of charged proteins. The model predicts the formation of multi-fractal structures with the geometry of the growth determined by the electrostatic interactions between single proteins. The model predictions are successfully verified in comparison with experimental curves for aggregate growth. The model is general and is able to predict aggregate morphologies occurring both in vivo and in vitro. Our findings provide for the first time a unifying and general framework where the physical interactions between single proteins, the aggregate morphology and the growth kinetics are connected into a single model in excellent agreement with the experimental data.