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  • Technical Review
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Atomic force microscopy-based mechanobiology

Nature Reviews Physics volume 1, pages 41–57 (2019)Cite this article

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Abstract

Mechanobiology emerges at the crossroads of medicine, biology, biophysics and engineering and describes how the responses of proteins, cells, tissues and organs to mechanical cues contribute to development, differentiation, physiology and disease. The grand challenge in mechanobiology is to quantify how biological systems sense, transduce, respond and apply mechanical signals. Over the past three decades, atomic force microscopy (AFM) has emerged as a key platform enabling the simultaneous morphological and mechanical characterization of living biological systems. In this Review, we survey the basic principles, advantages and limitations of the most common AFM modalities used to map the dynamic mechanical properties of complex biological samples to their morphology. We discuss how mechanical properties can be directly linked to function, which has remained a poorly addressed issue. We outline the potential of combining AFM with complementary techniques, including optical microscopy and spectroscopy of mechanosensitive fluorescent constructs, super-resolution microscopy, the patch clamp technique and the use of microstructured and fluidic devices to characterize the 3D distribution of mechanical responses within biological systems and to track their morphology and functional state.

Key points

  • The versatile functions of biological systems ranging from molecules, cells and cellular systems to living organisms are governed by their mechanical properties and ability to sense mechanical cues and respond to them.

  • Atomic force microscopy (AFM)-based approaches provide multifunctional nanotools to measure a wide variety of mechanical properties of living systems and to apply to them well-defined mechanical cues.

  • AFM allows us to apply and measure forces from the piconewton to the micronewton range on spatially defined areas with sizes ranging from the sub-nanometre to several tens of micrometres.

  • Mechanical parameters characterized by AFM include force, pressure, tension, adhesion, friction, elasticity, viscosity and energy dissipation.

  • The mechanical parameters of complex biological systems can be structurally mapped, with a spatial resolution ranging from millimetres to sub-nanometres and at kinetic ranges from hours to milliseconds.

  • AFM can be combined with various complementary methods to characterize a multitude of mechanical, functional and morphological properties and responses of complex biological systems.

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Fig. 1: Key operation modes of atomic force microscopy to quantitatively map the mechanical properties of biological systems.
Fig. 2: Probing, quantifying and mapping the mechanical properties of biological systems.
Fig. 3: Mapping the mechanical properties of cellular systems.
Fig. 4: Mapping the mechanical properties of microorganisms, viruses and blebbing cell membranes.
Fig. 5: High-resolution imaging and mapping of the mechanical properties of isolated membranes, proteins, fibrils and nucleic acids.

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Acknowledgements

The authors thank R. Newton for critically discussing the manuscript. M.K. acknowledges financial support from the Spanish Ministry of Economy and Competitiveness through the Ramon y Cajal programme (RYC-2015-17935), “Severo Ochoa” programme for the Centres of Excellence in R&D (SEV-2015-0522) from Fundació Privada Cellex, Generalitat de Catalunya, through the Centres de Recerca de Catalunya (CERCA) programme, and the European Research Council (ERC; MechanoSystems grant 715243). D.A. was supported by the ERC (NanoVirus grant 758224) and the National Fund for Scientific Research and Research Department of the Communauté française de Belgique (Concerted Research Action). B.M.G. was supported by a long-term European Molecular Biology Organization (EMBO) fellowship (ALTF 424–2016). W.H.R. was funded by the Nederlandse organisatie voor Wetenschappelijk Onderzoek (VIDI grant). H.E.G. acknowledges financial support from the CelluFuel ERC grant. C.G. was supported by the Swiss Nanoscience Institute (SNI), University of Basel. Y.F.D. was supported by the Université catholique de Louvain, ERC, under the European Union’s Horizon 2020 research and innovation programme (grant 693630), Walloon Excellence in Life Sciences and Biotechnology (WELBIO) (grant no. WELBIO-CR-2015A-05), National Fund for Scientific Research (FNRS and EOS grants) and Research Department of the Communauté française de Belgique (Concerted Research Action). D.J.M. was supported by the Swiss National Science Foundation (SNF; grant 310030B_160225), the National Centre of Competence in Research (NCCR) Molecular Systems Engineering and the Swiss Commission for Technology and Innovation (CTI, grant 28033.1).

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Authors and Affiliations

  1. Neurophotonics and Mechanical Systems Biology, Institute of Photonic Sciences (ICFO), Barcelona, Spain

    Michael Krieg

  2. Department of Biosystems Science and Engineering, Eidgenössische Technische Hochschule (ETH) Zürich, Basel, Switzerland

    Gotthold Fläschner, Benjamin M. Gaub & Daniel J. Müller

  3. Louvain Institute of Biomolecular Science and Technology, Université catholique de Louvain, Louvain-la-Neuve, Belgium

    David Alsteens & Yves F. Dufrêne

  4. Moleculaire Biofysica, Zernike Instituut, Rijksuniversiteit Groningen, Groningen, Netherlands

    Wouter H. Roos

  5. Department of Physics and Astronomy, Vrije Universiteit Amsterdam, Amsterdam, Netherlands

    Gijs J. L. Wuite

  6. Applied Physics, Ludwig-Maximilians Universität (LMU) Munich, Munich, Germany

    Hermann E. Gaub

  7. Swiss Nanoscience Institute (SNI), Institute of Physics, University of Basel, Basel, Switzerland

    Christoph Gerber

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Krieg, M., Fläschner, G., Alsteens, D. et al. Atomic force microscopy-based mechanobiology. Nat Rev Phys 1, 41–57 (2019). https://doi.org/10.1038/s42254-018-0001-7

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