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

Abstract

The kinetics of adsorption at the air/buffer solution interface of amyloid beta peptide, Aβ(1–42), whose bulk concentration (submicromolar) is more than two 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 Aβ adsorption at the interface. The duration of the lag phase was found to be highly dependent on both the Aβ 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 Aβ bulk concentration. Attenuated total reflection-IR spectra of the adsorbed Aβ transferred to a solid substrate and circular dichroism measurements of Aβ in the solution layer near the interface reveal that the natively unstructured Aβ in the bulk undergo a conformation change (folding) to mainly the α-helical structure. The results suggest that, prior to the adsorption step, an equilibrium between Aβ conformations is established within the subsurface. The kinetic equation derived from this model confirms that the overall Aβ adsorption is kinetically controlled and the apparent rate constant is proportional to the Aβ bulk concentration. This model also indicates that interfaces such as cell membranes and lipid bilayers may facilitate Aβ aggregation/fibrillation by providing a thin hydrophobic layer adjacent to the interface for the initial Aβ conformation change (misfolding) and accumulation. Such a preconcentration effect offers a plausible explanation of the fact that Aβ fibrillation occurs in vivo at nanomolar concentrations. Another important biological implication from our work is that Aβ 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.

Combined Effects of Agitation, Macromolecular Crowding, and Interfaces on Amyloidogenesis

“…Since amyloid-forming monomers are surface active, they have to diffuse to the surface layer (AWI) to be fibrilized (Fig. 6A), as was previously demonstrated experimentally (13)(14)(15)(16)(17)(18). Let m(z,t) denotes the mass density of the monomers in solution at position z, the equation that describes the time evolution of this mass density under diffusion is in Equation 9, …”

“…Because of their amphiphilic character, these amyloid-forming peptides adsorb at an air-water interface (AWI; non-polar gas and polar aqueous solution) or more generally at hydrophobic-hydrophilic interfaces (HHI; gas-liquid, solid-liquid, or membranes) (9 -14). Adsorption to HHI allows these amyloid-forming peptides to spatially concentrate, to align their side chains with polar and non-polar side-chains segregating on opposite sides of the ␤-strand, and ultimately to promote their assembly into amyloid species (13)(14)(15)(16)(17)(18).…”

Ca2+ Interacts with Glu-22 of Aβ(1–42) and Phospholipid Bilayers to Accelerate the Aβ(1–42) Aggregation Below the Critical Micelle Concentration

“…41 It is wellknown that outside the cell membrane a thin, nanometer-sized solution layer exists whose dielectric constant is 10 times less than that of the extracellular matrix. 20,32,72,73 Such a situation is also applicable to the lipid bilayer/solution interface. The substantially decreased dielectric constant facilitates the conversion of the unstructured Aβ(1−42) monomers to β-sheet-containing structures such as dimers.…”

Biochemistry of Amyloid -Protein and Amyloid Deposits in Alzheimer Disease

“…The interface between the interstitial fluid phase and the surface of the plasma membrane is likely to be a critical factor in influencing the aggregation pathway of Ab. A number of in vitro studies find this, showing interface clustering of Ab (Chi et al 2010) that slows the lag phase of fibril formation (Hellstrand et al 2010) by providing an environment for a hydrophobic layer adjacent to the membrane interface (Jiang et al 2009b). Physical movement/agitation at the watermembrane interface may also promote fibrillogenesis (Morinaga et al 2010;Wu et al 2010a).…”