Sub-molecular features of single proteins in solution resolved with scanning tunneling microscopy

Scanning tunneling microscopy (STM) can be used to image individual biological molecules, such as proteins, in vacuum or air. This requires sample dehydration and thus may not reflect the native state of the molecule. Extensive efforts have been made to image single proteins in solution using STM; however, the images have revealed only round or oval shapes with no sub-molecular details. Here, we present the sub-molecular features of streptavidin proteins under physiological conditions using a homebuilt low-leakage-current and highstability liquid phase STM. The N-lobe, C-lobe, and C-terminal tail of the epidermal growth factor receptor kinase domains were also resolved in solution. Our results demonstrate that the structure, morphology, and dynamics of a protein molecule can be examined under physiological conditions by the STM. [Figure not available: see fulltext.] © 2016, Tsinghua University Press and Springer-Verlag Berlin Heidelberg.