We use Fluorescence Lifetime Imaging Microscopy (FLIM) and Second Harmonic Imaging Microscopy (SHIM) to
investigate the fundamental molecular mechanisms responsible for nucleation and growth of amyloidogenic-derived
nanomaterials. The nanomaterials are assembled from of Amyloid-β(16-22), specifically Ac-KLVFFAE-NH2, the
nucleating core of the Alzheimer's Amyloid-β protein. We describe how FLIM and SHIM can be used to follow
different nucleation pathways and to quantify structural heterogeneities within these complex nanomaterials. New
evidence suggests that different structures emerge from distinct nucleation pathways and these insights inform our
understanding of the peptide self-assembly mechanisms. We discuss these insights in the context of a top down
understanding of amyloidogenic diseases, the bottom up control of functional nanomaterials and the discovery of realtime
structural indicators for nanofabrication strategies.
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