REFERENCES AND NOTES

to structural analysis, including other ferritins that could not be solved by x-ray crystallography. During the first 4 e–/Å2 on gold substrates, 1 to 2 Å of in-plane motion remain. These first few electrons are critical, as they potentially contain the most high-resolution information (26, 27). Future work will focus on substrate design and image acquisition conditions to reduce the initial motion even more. Along with further improve-ments in electron detector efficiency, this will bring cryo-EM to the physical limits imposed by the homogeneity of the protein preparation, the electron scattering cross sections of the bio-logical specimen (4), and the counting statistics of detecting individual electrons. We anticipat