Abstract
The nucleation and growth mechanisms in amyloid forming materials are of high interest due to their importance in human diseases and also due to their potential applications as functional nano-materials. While much is known about the β-sheet secondary structure of amyloids, the nucleation mechanism and self-assembly processes remain poorly understood. Multiple intermediate species have been proposed to play important roles in the self assembly process, yet these states remain poorly defined or have not been unambiguously identified in solution. We have used single molecule fluorescence spectroscopy and two-photon fluorescence imaging to investigate the earliest events in amyloid nucleation and growth. The combined use of imaging, fluctuation spectroscopy (FCS), lifetime microscopy (FLIM), and energy transfer (FRET) measurements has allowed us to directly observe in real time the intermediate states that form in solution, which ultimately lead to nucleation and growth of amyloid structures. These observations have demonstrated that unstructured protein aggregates play a key role in the earliest phases of self assembly.
© 2009 APS DLS
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