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Observing single biomolecules at work with the atomic force microscope

Nature Structural Biology volume 7, pages 715–718 (2000)Cite this article

Abstract

Progress in the application of the atomic force microscope (AFM) to imaging and manipulating biomolecules is the result of improved instrumentation, sample preparation methods and image acquisition conditions. Biological membranes can be imaged in their native state at a lateral resolution of 0.5–1 nm and a vertical resolution of 0.1–0.2 nm. Conformational changes that are related to functions can be resolved to a similar resolution, complementing atomic structure data acquired by other methods. The unique capability of the AFM to directly observe single proteins in their native environments provides insights into the interactions of proteins that form functional assemblies. In addition, single molecule force spectroscopy combined with single molecule imaging provides unprecedented possibilities for analyzing intramolecular and intermolecular forces. This review discusses recent examples that illustrate the power of AFM.

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Figure 1: Surface topograph of the major intrinsic proteins (MIP) from lens fiber cells recorded in buffer22.
Figure 2: Quantitative analyses of the native cytoplasmic purple membrane surface.
Figure 3: RNA polymerase at work34.
Figure 4: Conformational change and single molecule force spectroscopy of the HPI layer38,47.
Figure 5: Conformational changes of porin OmpF18.

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Acknowledgements

We gratefully thank D. Fotiadis for Fig. 1 and H. Hansma for the time-lapse series shown in Fig. 3. This work was supported by the Maurice E. Müller Foundation of Switzerland, and the Swiss National Foundation for Scientific Research.

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Authors and Affiliations

  1. M.E. Müller Institute for Structural Biology, Biozentrum, CH-4056, Basel, Switzerland

    Andreas Engel & Daniel J. Müller

  2. Max-Planck-Institute of Molecular Cell Biology and Genetics, Dresden, D-01307, Germany

    Daniel J. Müller

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  1. Andreas Engel
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Correspondence to Andreas Engel.

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Engel, A., Müller, D. Observing single biomolecules at work with the atomic force microscope. Nat Struct Mol Biol 7, 715–718 (2000). https://doi.org/10.1038/78929

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