title: A Colloidal Description of Intermolecular Interactions Driving Fibril-Fibril Aggregation of a Model Amphiphilic Peptide.
abstract: We apply a kinetic analysis platform to study the intermolecular interactions underlying the colloidal stability of dispersions of charged amyloid fibrils consisting of a model amphiphilic peptide (RADA 16-I). In contrast to the aggregation mechanisms observed in the large majority of proteins and peptides, where several elementary reactions involving both monomers and fibrils are present simultaneously, the system selected in this work allows the specific investigation of the fibril-fibril aggregation process. We examine the intermolecular interactions driving the aggregation reaction at pH 2.0 by changing the buffer composition in terms of salt concentration, type of ion as well as type and concentration of organic solvent. The aggregation kinetics are followed by dynamic light scattering, and the experimental data are simulated by Smoluchowski population balance equations, which allow to estimate the energy barrier between two colliding fibrils in terms of the Fuchs stability ratio (W). When normalized on a dimensionless time weighted on the Fuchs stability ratio, the aggregation profiles under a broad range of conditions collapse on a single master curve, indicating that the buffer composition modifies the aggregation kinetics without affecting the aggregation mechanism. Our results show that the aggregation process does not occur under diffusion-limited conditions. Rather, the reaction rate is limited by the presence of an activation energy barrier that is largely dominated by electrostatic repulsive interactions. Such interactions could be reduced by increasing the concentration of salt, which induces charge screening, or the concentration of organic solvent, which affects the dielectric constant. It is remarkable that the dependence of the activation energy on the ionic strength can be described quantitatively in terms of charge screening effects in the frame of the DLVO theory, although specific anion and cation effects are also observed. While anion effects are mainly related to the binding to the positive groups of the fibril surface and to the resulting decrease of the surface charge, cation effects are more complex and involve additional solvation forces.
authors.affiliation: Institute for Chemical and Bioengineering, Department of Chemistry and Applied Biosciences, ETH Zurich, Zurich 8093, Switzerland.
authors.forename: Marta
authors.initials: M
authors.lastname: Owczarz
authors.affiliation: Institute for Chemical and Bioengineering, Department of Chemistry and Applied Biosciences, ETH Zurich, Zurich 8093, Switzerland.
authors.forename: Anna C
authors.initials: AC
authors.lastname: Motta
authors.affiliation: Institute for Chemical and Bioengineering, Department of Chemistry and Applied Biosciences, ETH Zurich, Zurich 8093, Switzerland.
authors.forename: Massimo
authors.initials: M
authors.lastname: Morbidelli
authors.affiliation: Institute for Chemical and Bioengineering, Department of Chemistry and Applied Biosciences, ETH Zurich, Zurich 8093, Switzerland.
authors.forename: Paolo
authors.initials: P
authors.lastname: Arosio
mesh_terms: D000682:Amyloid / Q000737:chemistry*; D003102:Colloids / Q000737:chemistry; D004058:Diffusion; D004573:Electrolytes / Q000737:chemistry; D007700:Kinetics; D008958:Models, Molecular; D010455:Peptides / Q000737:chemistry*; D013501:Surface-Active Agents / Q000737:chemistry*
chemical_list: D000682:Amyloid; D003102:Colloids; D004573:Electrolytes; D010455:Peptides; D013501:Surface-Active Agents