Sabaté Raimon, Estelrich Joan
Departament de Fisicoquímica, Facultat de Farmàcia, Universitat de Barcelona, Barcelona (Catalonia, Spain).
Langmuir. 2005 Jul 19;21(15):6944-9. doi: 10.1021/la050472x.
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.
β-淀粉样肽（Aβ）以纤维状形式存在，是老年斑的主要成分，而老年斑是阿尔茨海默病的一个决定性特征。在溶液分析中，纤维形成表现出一个延迟期，这被解释为一个依赖成核/凝聚的过程。纤维生成动力学由两个关键参数控制：成核和伸长速率常数。我们通过测量肽聚集体引起的散射来表征Aβ纤维形成的时间进程。我们在此报告了Aβ与三种烷基溴化铵（十二烷基、十四烷基和十六烷基）在高于和低于胶束浓度时的相互作用及其对动力学常数的影响。我们观察到一种双重行为：表面活性剂以浓度依赖的方式促进或抑制纤维形成。在确定的表面活性剂浓度以下（接近无肽介质中相应的临界胶束浓度），表面活性剂可能通过破坏天然构象的静电相互作用促进聚集。超过该浓度，单体的稳定作用占主导。一般来说，表面活性剂会延迟但不会完全抑制聚集。
