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Electrostatics controls the formation of amyloid superstructures in protein aggregation.


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Authors

Foderà, Vito 
Zaccone, Alessio 
Lattuada, Marco 
Donald, Athene M 

Abstract

The possibility for proteins to aggregate in different superstructures, i.e. large-scale polymorphism, has been widely observed, but an understanding of the physicochemical 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 multifractal 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 allowing us to reveal the mechanism of formation of such complex structures. The model is general and is able to predict aggregate morphologies occurring both in vivo and in vitro. Our findings provide a framework where the physical interactions between single proteins, the aggregate morphology, and the growth kinetics are connected into a single model in agreement with the experimental data.

Description

Keywords

Amyloid, Biophysical Phenomena, Models, Chemical, Protein Aggregates, Static Electricity, Thermodynamics

Journal Title

Phys Rev Lett

Conference Name

Journal ISSN

0031-9007
1079-7114

Volume Title

111

Publisher

American Physical Society (APS)
Sponsorship
Engineering and Physical Sciences Research Council (EP/H006028/1)
Funding from the Engineering and Physical Sciences Research Council (EP/H004939/1), the Swiss National Science Foundation (Grants Nr. PBEZP2-131153 and Nr. 200020-126487/1) is gratefully acknowledged. A.Z. acknowledges support from the Ernest Oppenheimer Fellowship at Cambridge.