Super‐Resolution Imaging of Amyloid Structures over Extended Times by Using Transient Binding of Single Thioflavin T Molecules
Oligomeric amyloid structures are crucial therapeutic targets in Alzheimer's and other amyloid diseases. However, these oligomers are too small to be resolved by standard light microscopy. We have developed a simple and versatile tool to image amyloid structures by using thioflavin T without the need for covalent labeling or immunostaining. The dynamic binding of single dye molecules generates photon bursts that are used for fluorophore localization on a nanometer scale. Thus, photobleaching cannot degrade image quality, allowing for extended observation times. Super‐resolution transient amyloid binding microscopy promises to directly image native amyloid by using standard probes and record amyloid dynamics over minutes to days. We imaged amyloid fibrils from multiple polypeptides, oligomeric, and fibrillar structures formed during different stages of amyloid‐β aggregation, as well as the structural remodeling of amyloid‐β fibrils by the compound epi‐gallocatechin gallate.
Spehar, Kevin; Ding, Tianben; Sun, Yuanzi; Kedia, Niraja; Lu, Jin; Nahass, George R.; Lew, Matthew D.; and Bieschke, Jan, "Super‐Resolution Imaging of Amyloid Structures over Extended Times by Using Transient Binding of Single Thioflavin T Molecules" (2018). Electrical & Systems Engineering Publications and Presentations. 1.
Amino Acids, Peptides, and Proteins Commons, Analytical, Diagnostic and Therapeutic Techniques and Equipment Commons, Bioimaging and Biomedical Optics Commons, Optics Commons, Physical Chemistry Commons
This is the accepted version of the following article: Spehar K, Ding T, Sun Y, Kedia N, Lu J, Nahass GR, Lew MD, Bieschke J. Super‐resolution Imaging of Amyloid Structures over Extended Times by Using Transient Binding of Single Thioflavin T Molecules Chembiochem : a European journal of chemical biology. 2018; which has been published in final form at https://doi.org/10.1002/cbic.201800352. This article may be used for non-commercial purposes in accordance with the Wiley Self-Archiving Policy [olabout.wiley.com/WileyCDA/Section/id-820227.html].