title: Electrostatics controls the formation of amyloid superstructures in protein aggregation.
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.
authors.affiliation: Sector of Biological and Soft Systems, Department of Physics, Cavendish Laboratory, University of Cambridge, JJ Thomson Avenue, Cambridge CB3 0HE, United Kingdom.
authors.forename: Vito
authors.initials: V
authors.lastname: Foderà
authors.affiliation: Sector of Biological and Soft Systems, Department of Physics, Cavendish Laboratory, University of Cambridge, JJ Thomson Avenue, Cambridge CB3 0HE, United Kingdom and Theory of Condensed Matter, Department of Physics, Cavendish Laboratory, University of Cambridge, JJ Thomson Avenue, Cambridge CB3 0HE, United Kingdom.
authors.forename: Alessio
authors.initials: A
authors.lastname: Zaccone
authors.affiliation: ETH Institute for Chemical and Bioengineering, HCI F135, Wolfgang Pauli Strasse 10, 8093 Zurich, Switzerland.
authors.forename: Marco
authors.initials: M
authors.lastname: Lattuada
authors.affiliation: Sector of Biological and Soft Systems, Department of Physics, Cavendish Laboratory, University of Cambridge, JJ Thomson Avenue, Cambridge CB3 0HE, United Kingdom.
authors.forename: Athene M
authors.initials: AM
authors.lastname: Donald
mesh_terms: D000682:Amyloid / Q000737:chemistry*; D055592:Biophysical Phenomena; D008956:Models, Chemical; D066329:Protein Aggregates; D055672:Static Electricity; D013816:Thermodynamics
chemical_list: D000682:Amyloid; D066329:Protein Aggregates