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Imaging modes of atomic force microscopy for application in molecular and cell biology

Nature Nanotechnology volume 12, pages 295–307 (2017)Cite this article

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Abstract

Atomic force microscopy (AFM) is a powerful, multifunctional imaging platform that allows biological samples, from single molecules to living cells, to be visualized and manipulated. Soon after the instrument was invented, it was recognized that in order to maximize the opportunities of AFM imaging in biology, various technological developments would be required to address certain limitations of the method. This has led to the creation of a range of new imaging modes, which continue to push the capabilities of the technique today. Here, we review the basic principles, advantages and limitations of the most common AFM bioimaging modes, including the popular contact and dynamic modes, as well as recently developed modes such as multiparametric, molecular recognition, multifrequency and high-speed imaging. For each of these modes, we discuss recent experiments that highlight their unique capabilities.

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Figure 1: Timeline of key inventions, starting from the birth of AFM in 1986 to the latest AFM imaging modes in molecular and cell biology.
Figure 2: AFM-based imaging of native biological systems to molecular resolution.
Figure 3: Force–distance curve-based AFM.
Figure 4: Multifrequency AFM.
Figure 5: HS-AFM filming proteins in action.
Figure 6: AFM of cellular systems.

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Acknowledgements

Y.F.D. was supported by the Université catholique de Louvain, the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme (grant agreement no. 693630), the WELBIO (grant no. WELBIO-CR-2015A-05), the National Fund for Scientific Research (FNRS), the Federal Office for Scientific, Technical and Cultural Affairs (Interuniversity Poles of Attraction Programme) and the Research Department of the Communauté française de Belgique (Concerted Research Action). D.A. and D.M.M. were supported by the European Molecular Biology Organization (EMBO; ALTF 265-2013 and ALTF 506-2012). D.J.M. was supported by the Swiss National Science Foundation (SNF; grants 205320_160199 and 310030B_160225), the NCCR Molecular Systems Engineering and the Swiss Commission for Technology and Innovation (CTI; grant 17970.1). C.G. was supported by the Swiss Nano Institute (SNI) of the University of Basel. R.G. acknowledges financial support from the European Research Council AdG no. 340177 and the Ministerio de Economia y Competitividad MAT2016-76507-R. T.A. was supported by the Japan Society for the Promotion of Science (JSPS; grants 24227005 and 26119003) and by the Japan Science and Technology Agency (JST; CREST program on Structural Life Science and Advanced Core Technology for Innovative Life Science Research).

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Authors and Affiliations

  1. Institute of Life Sciences and Walloon Excellence in Life Sciences and Biotechnology (WELBIO), Université catholique de Louvain, Croix du Sud 4-5, bte L7.07.06., Louvain-la-Neuve, B-1348, Belgium

    Yves F. Dufrêne & David Alsteens

  2. Department of Physics, Kanazawa University, Kanazawa, 920-1192, Japan

    Toshio Ando

  3. Instituto de Ciencia de Materiales de Madrid, CSIC, Sor Juana Inés de la Cruz 3, Madrid, 28049, Spain

    Ricardo Garcia

  4. Department of Biosystems Science and Engineering, Eidgenössische Technische Hochschule (ETH) Zürich, Mattenstrasse 28, Basel, 4056, Switzerland

    David Martinez-Martin & Daniel J. Müller

  5. Department of BioNanoscience, Delft University of Technology, Van der Maasweg 9, Delft, 2629 HZ, The Netherlands

    Andreas Engel

  6. Swiss Nanoscience Institute, University of Basel, Klingelbergstrasse 80, Basel, 4057, Switzerland

    Christoph Gerber

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  1. Yves F. Dufrêne
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Correspondence to Yves F. Dufrêne or Daniel J. Müller.

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Dufrêne, Y., Ando, T., Garcia, R. et al. Imaging modes of atomic force microscopy for application in molecular and cell biology. Nature Nanotech 12, 295–307 (2017). https://doi.org/10.1038/nnano.2017.45

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