Mass Mapping of Amyloid Fibrils in the Electron Microscope Using STEM Imaging

Scanning transmission electron microscopy (STEM) in the dark-field mode of operation is a technique regularly used to record high-contrast images from isolated macromolecular assemblies at nanometer resolution. Dark-field STEM images are unique in that they can be readily quantified to provide information on the mass of individual molecular complexes. Importantly, because STEM images contain simultaneous mass and overall molecular shape information, the concept of “mass mapping” can be realized to provide distinctive measurements of the mass per area of planar assemblies or the mass per length of filamentous structures. In this chapter we describe how the STEM technique can be applied to generate characteristic measurements of mass per length from isolated Alzheimer’s amyloid fibrils.