Stimulatory and inhibitory effects of alkyl bromide surfactants on beta-amyloid fibrillogenesis.
Beta-amyloid peptide (Abeta), in fibrillar form, is the primary constituent of senile plaques, a defining feature of Alzheimer's disease. In solution assays, fibril formation exhibits a lag time, interpreted as a nucleation/condensation-dependent process. The kinetics of fibrillogenesis is controlled by two key parameters: nucleation and elongation rate constants. We characterized the time course of Abeta fibril formation by measuring the scattering caused by peptide aggregates. We report here the interaction of Abeta with three alkylammonium bromides (dodecyl, tetradecyl, and hexadecyl) at supra- and submicellar concentrations and their influence on the kinetic constants. We observed a dual behavior: surfactants promoted or retarded fibril formation in a concentration-dependent manner. Below a determined surfactant concentration (close to the corresponding critical micellar concentration in medium without peptide), surfactants favor aggregation, presumably by means of electrostatic interactions that destabilize the native conformation. Beyond such concentration, the stabilizing effects of the monomer predominate. As a general rule, surfactants delay but do not completely inhibit aggregation.
Sabaté
Raimon
R
Departament de Fisicoquímica, Facultat de Farmàcia, Universitat de Barcelona, Barcelona (Catalonia, Spain).
Estelrich
Joan
J
D016229:Amyloid beta-Peptides / Q000737:chemistry; D001704:Biopolymers; D001965:Bromides / Q000737:chemistry*; D007700:Kinetics; D013501:Surface-Active Agents / Q000737:chemistry*
D016229:Amyloid beta-Peptides; D001704:Biopolymers; D001965:Bromides; D013501:Surface-Active Agents