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Handbook of Single-Molecule Biophysics pp 449–485Cite as

Probing Single Membrane Proteins by Atomic Force Microscopy

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Abstract

In this book chapter, we describe the working principle of the atomic force microscope (AFM), followed by the applications of AFM in high-resolution imaging and single-molecule force spectroscopy of membrane proteins. In the imaging mode, AFM allows observing the assembly of membrane proteins directly in native membranes approaching a resolution of ~0.5 nm with an outstanding signal-to-noise ratio. Conformational deviations of individual membrane proteins can be observed and their functional states directly imaged. Time-lapse AFM can image membrane proteins at work. In conjunction with high- resolution imaging, the use of the AFM as a single-molecule force spectroscope (SMFS) has gained tremendous importance in recent years. This combination allows to locate the inter- and intramolecular interactions of single membrane proteins. SMFS allows characterization of interactions that guide the folding of proteins and describe the parameters that lead to their destabilization, malfunction and misfolding. Moreover, it enables to measure the interactions established by ligand- and inhibitor-binding and in membrane protein assemblies. Because of its practical use in characterizing various parameters of membrane proteins in their native environment, AFM can be aptly described as a ‘lab on a tip’ device.

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Authors and Affiliations

  1. Institut Curie, UMR168-CNRS, 26 Rue d’Ulm, 75248 Paris, France

    S. Scheuring, K. Tanuj Sapra & Daniel J. Müller

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  1. Institut für Biophysik, Universität Linz, Altenberger Straße 69, Linz, 4040, Austria

    Peter Hinterdorfer

  2. Harvard Medical School, Harvard University, Longwood Ave. 250, Boston, 02115, U.S.A.

    Antoine Oijen

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Scheuring, S., Sapra, K.T., Müller, D.J. (2009). Probing Single Membrane Proteins by Atomic Force Microscopy. In: Hinterdorfer, P., Oijen, A. (eds) Handbook of Single-Molecule Biophysics. Springer, New York, NY. https://doi.org/10.1007/978-0-387-76497-9_16

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