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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.

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Publication history

Received: 15 February 2016
Revised: 06 May 2016
Accepted: 09 May 2016
Published: 15 June 2016
Issue date: September 2016

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© Tsinghua University Press and Springer‐Verlag Berlin Heidelberg 2016

Acknowledgements

Acknowledgements

This work was supported by the Chinese Academy of Sciences "Hundred Talent program" and National Natural Science Foundation of China (No. U1532151) to X. Z. and by Chinese national high magnetic field facilities, the Fundamental Research Funds for the Central Universities (No. WK2340000035) and National Natural Science Foundation of China (Nos. U1232210, 11204306, and 11374278) to Q. Y. L.

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Email: nanores@tup.tsinghua.edu.cn

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