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Characterization of the motion of membrane proteins using high-speed atomic force microscopy

Nature Nanotechnology volume 7, pages 525529 (2012) | Download Citation

Abstract

For cells to function properly1, membrane proteins must be able to diffuse within biological membranes. The functions of these membrane proteins depend on their position and also on protein–protein and protein–lipid interactions2. However, so far, it has not been possible to study simultaneously the structure and dynamics of biological membranes. Here, we show that the motion of unlabelled membrane proteins can be characterized using high-speed atomic force microscopy3. We find that the molecules of outer membrane protein F (OmpF) are widely distributed in the membrane as a result of diffusion-limited aggregation, and while the overall protein motion scales roughly with the local density of proteins in the membrane, individual protein molecules can also diffuse freely or become trapped by protein–protein interactions. Using these measurements, and the results of molecular dynamics simulations, we determine an interaction potential map and an interaction pathway for a membrane protein, which should provide new insights into the connection between the structures of individual proteins and the structures and dynamics of supramolecular membranes.

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Acknowledgements

The authors thank C. Nimigean and F. Rico for critical discussion of the manuscript. The authors also thank P. Abeyrathne for support with the lipopolysaccharide detection. Work in the Scheuring laboratory was supported by the Institut Curie, the Institut National de la Santé et Recherche Médicale (INSERM), the Agence Nationale de la Recherche (ANR) and the City of Paris. Work in the Sturgis laboratory was supported by the Centre National de la Recherche Scientifique (CNRS), the Agence Nationale de la Recherche (ANR), Centre Informatique National de l'Enseignement Superieur (CINES) and Aix-Marseille University. Work in the Stahlberg laboratory was supported by the Swiss National Science Foundation (grant no. 315230_127545, and NCCRs Struct Biol and TransCure) and the Swiss Initiative for Systems Biology (SystemsX.ch).

Author information

Affiliations

  1. U1006 INSERM, Aix-Marseille Université, Parc Scientifique et Technologique de Luminy, 163 avenue de Luminy, 13009 Marseille, France

    • Ignacio Casuso
    • , Mohamed Husain
    •  & Simon Scheuring
  2. UPR-9027 LISM, CNRS-Aix-Marseille University, Marseille, 13402, France

    • Jonathan Khao
    • , Jean-Pierre Duneau
    •  & James N. Sturgis
  3. Center for Cellular Imaging and NanoAnalytics (C-CINA), Biozentrum, University Basel, Mattenstrasse 26, WRO-1058, CH-4058 Basel, Switzerland

    • Mohamed Chami
    •  & Henning Stahlberg
  4. Cell and Tissue Imaging Facility (PICT-IBiSA), UMR144 CNRS-Institut Curie, 26 rue d'Ulm, Paris, F-75248 France

    • Perrine Paul-Gilloteaux

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Contributions

I.C. and S.S. conceived the experiments. I.C., M.H., M.C. and J.K. performed experiments. I.C., S.S., M.H., P.P-G., J-P.D. and J.N.S. analysed the data. I.C., S.S., J.N.S. and H.S. co-wrote the paper.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Simon Scheuring.

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DOI

https://doi.org/10.1038/nnano.2012.109

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