More recent studies of amyloid fibrils have focused on defining local structural information on β-sheet packing using X-ray fibre diffraction, solid-state NMR, and electron paramagnetic resonance spectroscopy.12–15 High resolution models for fibril core structures have recently been provided based on tightly packed β-sheets in three-dimensional (3D) crystals of short peptides,16,17 as well as assemblies built from parallel arrays of in-register β-strands in β-helical or serpentine arrangements.6 While these studies provide detailed information about local packing within the cross-β core, the larger scale assembly of amyloid fibrils is not well understood. For example, it is still unclear how protein subunits assemble into protofilaments and what determines protofilament assembly into fibrils. Because of the structural heterogeneity of fibril preparations seen by electron microscopy (EM) and atomic force microscopy, it is unlikely that these questions can be addressed by measurements on bulk samples. Different fibrils within a population contain different numbers of protofilaments and variable twists ranging from flat ribbons to tubular arrangements of protofilaments. This range of structures is typically seen within a single sample.18–20