Functionalized Mesoporous Silicas Direct Structural
Polymorphism of Amyloid‑β Fibrils
Posted on 2020-06-16 - 19:33
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.
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Lucas, Michael
J.; Pan, Henry S.; Verbeke, Eric J.; Webb, Lauren J.; Taylor, David W.; Keitz, Benjamin K. (2020). Functionalized Mesoporous Silicas Direct Structural
Polymorphism of Amyloid‑β Fibrils. ACS Publications. Collection. https://doi.org/10.1021/acs.langmuir.0c00827