Functionalized Mesoporous Silicas Direct Structural Polymorphism of Amyloid‑β Fibrils

• Published in: Langmuir Vol. 36; no. 26; pp. 7345 - 7355
• Main Authors: Lucas, Michael J, Pan, Henry S, Verbeke, Eric J, Webb, Lauren J, Taylor, David W, Keitz, Benjamin K
• Format: Journal Article
• Language: English
• Published: American Chemical Society 07.07.2020
• ISSN: 0743-7463; 1520-5827
• DOI: 10.1021/acs.langmuir.0c00827

The aggregation of amyloid-β (Aβ) is associated with the onset of Alzheimer’s disease (AD) and involves a complex kinetic pathway as monomers self-assemble into fibrils. A central feature of amyloid fibrils is the existence of multiple structural polymorphs, which complicates the development of disease-relevant structure–function relationships. Developing these relationships requires new methods to control fibril structure. In this work, we evaluated the effect that mesoporous silicas (SBA-15) functionalized with hydrophobic (SBA-PFDTS) and hydrophilic groups (SBA-PEG) have on the aggregation kinetics and resulting structure of Aβ1–40 fibrils. The hydrophilic SBA-PEG had little effect on amyloid kinetics, while as-synthesized and hydrophobic SBA-PFDTS accelerated aggregation kinetics. Subsequently, we quantified the relative population of fibril structures formed in the presence of each material using electron microscopy. Fibrils formed from Aβ1–40 exposed to SBA-PEG were structurally similar to control fibrils. In contrast, Aβ1–40 incubated with SBA-15 or SBA-PFDTS formed fibrils with shorter crossover distances that were more structurally representative of fibrils found in AD patient derived samples. Overall, our results suggest that mesoporous silicas and other exogenous materials are promising scaffolds for the de novo production of specific fibril polymorphs of Aβ1–40 and other amyloidogenic proteins.