A Kinetic Model for β-Amyloid Adsorption at the Air/Solution Interface and Its Implication to the β-Amyloid Aggregation Process

At the air/buffer solution interface the kinetics of adsorption of amyloid beta peptide, A beta(1-42), whose bulk concentration (submicromolar) is more than 2 orders of magnitude lower than that typically used in other in vitro aggregation studies, has been studied using a Langmuir-Blodgett trough. The pressure-time curves exhibit a lag phase, wherein the surface pressure essentially remains at zero, and a rising phase, corresponding to the A beta adsorption at the interface. The duration of the lag phase was found to be highly dependent on both the A beta bulk concentration and the solution temperature. A large activation energy (62.2 +/- 4.1 KJ/mol) was determined and the apparent adsorption rate constant was found to be linearly dependent on the A beta bulk concentration. Attenuated total reflection-IR spectra of the adsorbed A beta transferred to a solid substrate and circular dichroism measurements of A beta in the solution layer near the interface reveal that the natively unstructured A in the bulk undergo a conformation change (folding) to mainly the a-helical structure. The results suggest that, prior to the adsorption step, an equilibrium between A beta conformations is established within the subsurface. The kinetic equation derived from this model confirms that the overall A beta adsorption is kinetically controlled and the apparent rate constant is proportional to the A beta bulk concentration. This model also indicates that interfaces such as cell membranes and lipid bilayers may facilitate A beta aggregation/fibrillation by providing a thin hydrophobic layer adjacent to the interface for the initial A beta conformation change (misfolding) and accumulation. Such a preconcentration effect offers a plausible explanation of the fact that A beta fibrillation occurs in vivo at nanomolar concentrations. Another important biological implication from our work is that A beta misfolding may occur before its adsorption onto a cell membrane. This general kinetic model should also find applications in adsorption studies of other types of biomolecules whose overall kinetics exhibits a lag phase that is dependent on the bulk concentration of the adsorbate.