(16i) Influence of Porous Materials on Amyloid-? Protein Aggregation

The aggregation of amyloidogenic proteins is associated with a variety of neurodegenerative diseases. In particular, amyloid fibrils and oligomers formed from Amyloid-β (Aβ), play a key role in the progression of Alzheimer’s Disease. However, the aggregation pathway of Aβ is extremely complex, resulting in a structurally diverse population of fibrils, oligomers, and other aggregates. A better understanding of this mechanism in addition to the ability to direct amyloid formation is necessary for effective therapeutic design. Exogenous materials, such as hydrophobic surfaces, nanoparticles, and polymers, have been shown to influence amyloid formation in vitro and in vivo. To better understand how exogenous materials could direct amyloid formation, Aβ_1-40 was exposed to porous materials, specifically zeolites and mesoporous silica, allowing for us to study the combined effects of surface chemistry and porosity on the aggregation of Aβ. Through Thioflavin T fluorescence, we found that zeolite Y containing Na⁺, Mg²⁺, and Fe³⁺ ions increased the primary nucleation rate of Aβ. On the other hand, CuY and ZnY accelerated the formation of oligomeric intermediates, but overall inhibited the formation of fibrils, as evidenced by Western Blot and TEM. Additionally, seeding studies confirmed that ZnY and CuY oligomers were kinetically trapped in an inactive state. These findings were supported through measurements of binding affinity, in which ZnY and CuY exhibited higher association constants. We also examined the effect of SBA-15, which has pores large enough to encapsulate Aβ monomers and larger structures. Overall, our results show that porous materials can impact amyloid aggregation and speciation.