Aggregate Size Dependence of Amyloid Adsorption onto Charged Interfaces

Abstract

Amyloid aggregates are associated with a range of human neurodegenerative disorders, and it has been shown that neurotoxicity is dependent on aggregate size. Combining molecular simulation with analytical theory, a predictive model is proposed for the adsorption of amyloid aggregates onto oppositely charged surfaces, where the interaction is governed by an interplay between electrostatic attraction and entropic repulsion. Predictions are experimentally validated against quartz crystal microbalance–dissipation experiments of amyloid beta peptides and fragmented fibrils in the presence of a supported lipid bilayer. Assuming amyloids as rigid, elongated particles, we observe nonmonotonic trends for the extent of adsorption with respect to aggregate size and preferential adsorption of smaller aggregates over larger ones. Our findings describe a general phenomenon with implications for stiff polyions and rodlike particles that are electrostatically attracted to a surface.

Structure Determination of Hen Egg-White Lysozyme Aggregates Adsorbed to Lipid/Water and Air/Water Interfaces

“…23 Moreover, it was reported that smaller Aβ aggregates have preferential adsorption over the larger ones. 24 Small onpathway α-synuclein aggregates can insert into the negatively charged lipid bilayer and form larger coaggregates from protein and lipid, thus damaging the membrane irreversibly. 25 Several nonstructural methods are very useful to study the adsorption of protein aggregates, e.g., quartz crystal microbalance-dissipation, 24 atomic force microscopy, 26 impedance spectroscopy, 27 and others.…”

“…24 Small onpathway α-synuclein aggregates can insert into the negatively charged lipid bilayer and form larger coaggregates from protein and lipid, thus damaging the membrane irreversibly. 25 Several nonstructural methods are very useful to study the adsorption of protein aggregates, e.g., quartz crystal microbalance-dissipation, 24 atomic force microscopy, 26 impedance spectroscopy, 27 and others. However, the simultaneous structure determination of the adsorbed aggregates is necessary in order to acquire a full molecular picture.…”

“…For example, smaller oligomeric aggregates of Aβ were shown to exhibit a cytotoxic effect, while large fibrillar aggregates did not trigger cell injury . Moreover, it was reported that smaller Aβ aggregates have preferential adsorption over the larger ones . Small on-pathway α-synuclein aggregates can insert into the negatively charged lipid bilayer and form larger coaggregates from protein and lipid, thus damaging the membrane irreversibly …”

“…Several nonstructural methods are very useful to study the adsorption of protein aggregates, e.g. , quartz crystal microbalance-dissipation, atomic force microscopy, impedance spectroscopy, and others. However, the simultaneous structure determination of the adsorbed aggregates is necessary in order to acquire a full molecular picture.…”

Steady, Symmetric, and Reversible Growth and Dissolution of Individual Amyloid-β Fibrils

“…■ RESULTS AND DISCUSSION Determination of Fibril Growth Rates. We generate fibrils in a stirred solution and deposit them on freshly cleaved mica surfaces 72 mounted on the AFM scanner; please see the Methods section below. We fill the AFM fluid cell with an Aβ40 solution of known concentration in 40 mM phosphate buffer at pH = 7.4.…”