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Document Type
Article
Publication Date
3-13-2024
Abstract
Synthetic peptides that self-assemble into cross-β fibrils are versatile building blocks for engineered biomaterials due to their modularity and biocompatibility, but their structural and morphological similarities to amyloid species have been a long-standing concern for their translation. Further, their polymorphs are difficult to characterize using spectroscopic and imaging techniques that rely on ensemble averaging to achieve high resolution. Here, we utilize Nile red (NR), an amyloidophilic fluorogenic probe, and single-molecule orientation-localization microscopy (SMOLM) to characterize fibrils formed by the designed amphipathic enantiomers KFE8L and KFE8D and the pathological amyloid-beta peptide Aβ42. Importantly, NR SMOLM reveals the helical (bilayer) ribbon structure of both KFE8 and Aβ42 and quantifies the precise tilt of the fibrils’ inner and outer backbones in relevant buffer conditions without the need for covalent labeling or sequence mutations. SMOLM also distinguishes polymorphic branched and curved morphologies of KFE8 whose backbones exhibit much more heterogeneity than those of typical straight fibrils. Thus, SMOLM is a powerful tool to interrogate the structural differences and polymorphism between engineered and pathological cross β-rich fibrils.
Recommended Citation
Zhou, Weiyan; O'Neill, Conor L.; Ding, Tianben; Zhang, Oumeng; Rudra, Jai S.; and Lew, Matthew D., "Resolving the Nanoscale Structure of β-Sheet Peptide Self-Assemblies Using Single-Molecule Orientation–Localization Microscopy" (2024). Electrical & Systems Engineering Publications and Presentations. 17.
https://openscholarship.wustl.edu/ese_facpubs/17
Included in
Bioimaging and Biomedical Optics Commons, Biological and Chemical Physics Commons, Biomaterials Commons, Electrical and Computer Engineering Commons, Optics Commons
Comments
This document is the Accepted Manuscript version of a Published Work that appeared in final form in ACS Nano, copyright © 2024 American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see https://doi.org/10.1021/acsnano.3c11771.