Single Molecule Fluorescence Studies of Amyloid-Beta 1-42 Aggregation

The dynamic nature of amyloid beta (1-40) aggregation.

In this paper, we characterize the dynamic nature of the full amyloid beta (1-40) (Aβ (1-40)) aggregates. We labeled the peptide with either 5-carboxytetramethylrhodamine (TAMRA) or with fluorescein-isothiocyanate (FITC). The labeled peptides were mixed after separate fibrillization, and the dynamic changes in the structure of the fibrils were imaged using confocal microscopy. Fluorescence reso...

Heat shock proteins 70 and 90 inhibit early stages of amyloid beta-(1-42) aggregation in vitro.

Alzheimer disease is a neurological disorder that is characterized by the presence of fibrils and oligomers composed of the amyloid beta (Abeta) peptide. In models of Alzheimer disease, overexpression of molecular chaperones, specifically heat shock protein 70 (Hsp70), suppresses phenotypes related to Abeta aggregation. These observations led to the hypothesis that chaperones might interact wit...

Single-molecule fluorescence studies of Protein Folding and Molecular Chaperones

Folding of newly synthesized proteins is an essential part of protein biosynthesis and misfolding can result in protein aggregation which can also lead to several severe diseases. Protein folding is a highly heterogeneous process and rarely populated intermediate states may play an important role. Single-molecule techniques are ideally suited to resolve these heterogeneities. In this thesis, I ...

Single-molecule fluorescence studies of protein folding and conformational dynamics.

SnapShot: Single-Molecule Fluorescence

Common uorescent agents include organic uorophores (e.g., Cy5), uorescent proteins (e.g., GFP), and semiconductor quantum dots each with different size, photobleaching, blinking, and labeling ef ciency properties. Wideeld detection with EMCCD camera enables parallel measurements. The temporal resolution is >ms, and the working concentration is limited to nM or less. Confocal detection from an e...