Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Force probing surfaces of living cells to molecular resolution

Nature Chemical Biology volume 5, pages 383–390 (2009)Cite this article

Abstract

Biological processes rely on molecular interactions that can be directly measured using force spectroscopy techniques. Here we review how atomic force microscopy can be applied to force probe surfaces of living cells to single-molecule resolution. Such probing of individual interactions can be used to map cell surface receptors, and to assay the receptors' functional states, binding kinetics and landscapes. This information provides unique insight into how cells structurally and functionally modulate the molecules of their surfaces to interact with the cellular environment.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: AFM probing surfaces of living cells.
Figure 2: AFM-based single-cell force spectroscopy.
Figure 3: Force probing bonds at cell surfaces reveals their energetic and kinetic properties.
Figure 4: Localizing VE-cadherin domains on vascular endothelial cell surfaces.
Figure 5: Mapping hydrophobic forces on live cells.
Figure 6: Quantifying the adhesion between embryonic cells by SCFS.

Similar content being viewed by others

References

  1. Sheetz, M.P. Cell control by membrane-cytoskeleton adhesion. Nat. Rev. Mol. Cell Biol. 2, 392–396 (2001).

    Article  CAS  PubMed  Google Scholar 

  2. Gumbiner, B.M. Regulation of cadherin-mediated adhesion in morphogenesis. Nat. Rev. Mol. Cell Biol. 6, 622–634 (2005).

    Article  CAS  PubMed  Google Scholar 

  3. Discher, D.E., Janmey, P. & Wang, Y.L. Tissue cells feel and respond to the stiffness of their substrate. Science 310, 1139–1143 (2005).

    Article  CAS  PubMed  Google Scholar 

  4. Vogel, V. & Sheetz, M. Local force and geometry sensing regulate cell functions. Nat. Rev. Mol. Cell Biol. 7, 265–275 (2006).

    Article  CAS  PubMed  Google Scholar 

  5. Lecuit, T. & Lenne, P.F. Cell surface mechanics and the control of cell shape, tissue patterns and morphogenesis. Nat. Rev. Mol. Cell Biol. 8, 633–644 (2007).

    Article  CAS  PubMed  Google Scholar 

  6. Geiger, B., Bershadsky, A., Pankov, R. & Yamada, K.M. Transmembrane crosstalk between the extracellular matrix–cytoskeleton crosstalk. Nat. Rev. Mol. Cell Biol. 2, 793–805 (2001).

    Article  CAS  PubMed  Google Scholar 

  7. Israelachvili, J. Intermolecular & Surface Forces (Academic Press Limited, London, 1991).

    Google Scholar 

  8. Bustamante, C., Chemla, Y.R., Forde, N.R. & Izhaky, D. Mechanical processes in biochemistry. Annu. Rev. Biochem. 73, 705–748 (2004).

    Article  CAS  PubMed  Google Scholar 

  9. Chen, W., Evans, E.A., McEver, R.P. & Zhu, C. Monitoring receptor-ligand interactions between surfaces by thermal fluctuations. Biophys. J. 94, 694–701 (2008).

    Article  CAS  PubMed  Google Scholar 

  10. Tanase, M., Biais, N. & Sheetz, M. Magnetic tweezers in cell biology. Methods Cell Biol. 83, 473–493 (2007).

    Article  CAS  PubMed  Google Scholar 

  11. Moffitt, J.R., Chemla, Y.R., Smith, S.B. & Bustamante, C. Recent advances in optical tweezers. Annu. Rev. Biochem. 77, 205–228 (2008).

    Article  CAS  PubMed  Google Scholar 

  12. Neuman, K.C. & Nagy, A.K. Single-molecule force spectroscopy: optical tweezers, magnetic tweezers and atomic force microscopy. Nat. Methods 5, 491–505 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Binnig, G., Quate, C.F. & Gerber, C. Atomic force microscope. Phys. Rev. Lett. 56, 930–933 (1986).

    Article  CAS  PubMed  Google Scholar 

  14. Gerber, C. & Lang, H.P. How the doors to the nanoworld were opened. Nat. Nanotechnol. 1, 3–5 (2006).

    Article  CAS  PubMed  Google Scholar 

  15. Helenius, J., Heisenberg, C.P., Gaub, H.E. & Muller, D.J. Single-cell force spectroscopy. J. Cell Sci. 121, 1785–1791 (2008).

    Article  CAS  PubMed  Google Scholar 

  16. Müller, D.J. & Dufrêne, Y.F. Atomic force microscopy as a multifunctional molecular toolbox in nanobiotechnology. Nat. Nanotechnol. 3, 261–269 (2008).

    Article  PubMed  CAS  Google Scholar 

  17. Puchner, E.M. et al. Mechanoenzymatics of titin kinase. Proc. Natl. Acad. Sci. USA 105, 13385–13390 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. del Rio, A. et al. Stretching single talin rod molecules activates vinculin binding. Science 323, 638–641 (2009).

    Article  CAS  PubMed  Google Scholar 

  19. Drake, B. et al. Imaging crystals, polymers, and processes in water with the atomic force microscope. Science 243, 1586–1589 (1989).

    Article  CAS  PubMed  Google Scholar 

  20. Muller, D.J. & Engel, A. Atomic force microscopy and spectroscopy of native membrane proteins. Nat. Protoc. 2, 2191–2197 (2007).

    Article  PubMed  CAS  Google Scholar 

  21. Le Grimellec, C. et al. Imaging of the surface of living cells by low-force contact-mode atomic force microscopy. Biophys. J. 75, 695–703 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Sharma, A., Anderson, K.I. & Muller, D.J. Actin microridges characterized by laser scanning confocal and atomic force microscopy. FEBS Lett. 579, 2001–2008 (2005).

    Article  CAS  PubMed  Google Scholar 

  23. Dufrêne, Y.F. Towards nanomicrobiology using atomic force microscopy. Nat. Rev. Microbiol. 6, 674–680 (2008).

    Article  PubMed  CAS  Google Scholar 

  24. Plomp, M., Leighton, T.J., Wheeler, K.E., Hill, H.D. & Malkin, A.J. In vitro high-resolution structural dynamics of single germinating bacterial spores. Proc. Natl. Acad. Sci. USA 104, 9644–9649 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Franz, C.M. & Muller, D.J. Analysing focal adhesion structure by AFM. J. Cell Sci. 118, 5315–5323 (2005).

    Article  CAS  PubMed  Google Scholar 

  26. Lee, G.U., Kidwell, D.A. & Colton, R.J. Sensing discrete streptavidin-biotin interactions with atomic force microscopy. Langmuir 10, 354–357 (1994).

    Article  CAS  Google Scholar 

  27. Moy, V.T., Florin, E.-L. & Gaub, H.E. Intermolecular forces and energies between ligands and receptors. Science 266, 257–259 (1994).

    Article  CAS  PubMed  Google Scholar 

  28. Fritz, J., Katopodis, A.G., Kolbinger, F. & Anselmetti, D. Force-mediated kinetics of single P-selectin/ligand complexes observed by atomic force microscopy. Proc. Natl. Acad. Sci. USA 95, 12283–12288 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Baumgartner, W. et al. Cadherin interaction probed by atomic force microscopy. Proc. Natl. Acad. Sci. USA 97, 4005–4010 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Shi, Q., Chien, Y.H. & Leckband, D. Biophysical properties of cadherin bonds do not predict cell sorting. J. Biol. Chem. 283, 28454–28463 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Rief, M., Oesterhelt, F., Heymann, B. & Gaub, H.E. Single molecule force spectroscopy on polysaccharides by AFM. Science 275, 1295–1297 (1997).

    Article  CAS  PubMed  Google Scholar 

  32. Dammer, U. et al. Binding strength between cell adhesion proteoglycans measured by atomic force microscopy. Science 267, 1173–1175 (1995).

    Article  CAS  PubMed  Google Scholar 

  33. Kedrov, A., Janovjak, H., Sapra, K.T. & Muller, D.J. Deciphering molecular interactions of native membrane proteins by single-molecule force spectroscopy. Annu. Rev. Biophys. Biomol. Struct. 36, 233–260 (2007).

    Article  CAS  PubMed  Google Scholar 

  34. Kedrov, A., Appel, M., Baumann, H., Ziegler, C. & Muller, D.J. Examining the dynamic energy landscape of an antiporter upon inhibitor binding. J. Mol. Biol. 375, 1258–1266 (2008).

    Article  CAS  PubMed  Google Scholar 

  35. Junker, J.P., Ziegler, F. & Rief, M. Ligand-dependent equilibrium fluctuations of single calmodulin molecules. Science 323, 633–637 (2009).

    Article  CAS  PubMed  Google Scholar 

  36. Ganchev, D.N., Rijkers, D.T., Snel, M.M., Killian, J.A. & de Kruijff, B. Strength of integration of transmembrane alpha-helical peptides in lipid bilayers as determined by atomic force spectroscopy. Biochemistry 43, 14987–14993 (2004).

    Article  CAS  PubMed  Google Scholar 

  37. Bershadsky, A., Kozlov, M. & Geiger, B. Adhesion-mediated mechanosensitivity: a time to experiment, and a time to theorize. Curr. Opin. Cell Biol. 18, 472–481 (2006).

    Article  CAS  PubMed  Google Scholar 

  38. Hynes, R.O. Integrins: bidirectional, allosteric signaling machines. Cell 110, 673–687 (2002).

    Article  CAS  PubMed  Google Scholar 

  39. Rose, D.M., Alon, R. & Ginsberg, M.H. Integrin modulation and signaling in leukocyte adhesion and migration. Immunol. Rev. 218, 126–134 (2007).

    Article  CAS  PubMed  Google Scholar 

  40. Schmitt, L., Ludwig, M., Gaub, H.E. & Tampe, R. A metal-chelating microscopy tip as a new toolbox for single-molecule experiments by atomic force microscopy. Biophys. J. 78, 3275–3285 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Tinazli, A. et al. High-affinity chelator thiols for switchable and oriented immobilization of histidine-tagged proteins: a generic platform for protein chip technologies. Chemistry (Easton) 11, 5249–5259 (2005).

    CAS  Google Scholar 

  42. Hinterdorfer, P., Baumgartner, W., Gruber, H.J., Schilcher, K. & Schindler, H. Detection and localization of individual antibody-antigen recognition events by atomic force microscopy. Proc. Natl. Acad. Sci. USA 93, 3477–3481 (1996).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Jonkheijm, P., Weinrich, D., Schroder, H., Niemeyer, C.M. & Waldmann, H. Chemical strategies for generating protein biochips. Angew. Chem. Int. Edn. Engl. 47, 9618–9647 (2008).

    Article  CAS  Google Scholar 

  44. Rankl, C. et al. Multiple receptors involved in human rhinovirus attachment to live cells. Proc. Natl. Acad. Sci. USA 105, 17778–17783 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  45. Ebner, A. et al. A new, simple method for linking of antibodies to atomic force microscopy tips. Bioconjug. Chem. 18, 1176–1184 (2007).

    Article  CAS  PubMed  Google Scholar 

  46. Hsiao, S.C. et al. DNA-coated AFM cantilevers for the investigation of cell adhesion and the patterning of live cells. Angew. Chem. Int. Edn. Engl. 47, 8473–8477 (2008).

    Article  CAS  Google Scholar 

  47. Razatos, A., Ong, Y.L., Sharma, M.M. & Georgiou, G. Molecular determinants of bacterial adhesion monitored by atomic force microscopy. Proc. Natl. Acad. Sci. USA 95, 11059–11064 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Benoit, M., Gabriel, D., Gerisch, G. & Gaub, H.E. Discrete interactions in cell adhesion measured by single-molecule force spectroscopy. Nat. Cell Biol. 2, 313–317 (2000).

    Article  CAS  PubMed  Google Scholar 

  49. Humphries, J.D., Byron, A. & Humphries, M.J. Integrin ligands at a glance. J. Cell Sci. 119, 3901–3903 (2006).

    Article  CAS  PubMed  Google Scholar 

  50. Wojcikiewicz, E.P., Zhang, X., Chen, A. & Moy, V.T. Contributions of molecular binding events and cellular compliance to the modulation of leukocyte adhesion. J. Cell Sci. 116, 2531–2539 (2003).

    Article  CAS  PubMed  Google Scholar 

  51. Zhang, X., Wojcikiewicz, E. & Moy, V.T. Force spectroscopy of the leukocyte function-associated antigen-1/intercellular adhesion molecule-1 interaction. Biophys. J. 83, 2270–2279 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Fierro, F.A. et al. BCR/ABL expression of myeloid progenitors increases beta1-integrin mediated adhesion to stromal cells. J. Mol. Biol. 377, 1082–1093 (2008).

    Article  CAS  PubMed  Google Scholar 

  53. Friedrichs, J., Manninen, A., Muller, D.J. & Helenius, J. Galectin-3 regulates the kinetics of integrin alpha2beta1-mediated adhesion to collagen-I and -IV. J. Biol. Chem. 283, 32264–32272 (2008).

    Article  CAS  PubMed  Google Scholar 

  54. Taubenberger, A. et al. Revealing early steps of alpha2beta1 integrin-mediated adhesion to collagen type I by using single-cell force spectroscopy. Mol. Biol. Cell 18, 1634–1644 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Friedrichs, J. et al. Contributions of galectin-3 and -9 to epithelial cell adhesion analyzed by single cell force spectroscopy. J. Biol. Chem. 282, 29375–29383 (2007).

    Article  CAS  PubMed  Google Scholar 

  56. Li, F., Redick, S.D., Erickson, H.P. & Moy, V.T. Force measurements of the alpha5beta1 integrin-fibronectin interaction. Biophys. J. 84, 1252–1262 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Krieg, M., Helenius, J., Heisenberg, C.P. & Muller, D.J. A bond for a lifetime: employing membrane nanotubes from living cells to determine receptor-ligand kinetics. Angew. Chem. Int. Edn. Engl. 47, 9775–9777 (2008).

    Article  CAS  Google Scholar 

  58. Evans, E.A. & Calderwood, D.A. Forces and bond dynamics in cell adhesion. Science 316, 1148–1153 (2007).

    Article  CAS  PubMed  Google Scholar 

  59. Evans, E. Energy landscapes of biomolecular adhesion and receptor anchoring at interfaces explored with dynamic force spectroscopy. Faraday Discuss. 111, 1–16 (1998).

    Article  CAS  Google Scholar 

  60. Evans, E. & Ritchie, K. Dynamic strength of molecular adhesion bonds. Biophys. J. 72, 1541–1555 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Evans, E., Leung, A., Heinrich, V. & Zhu, C. Mechanical switching and coupling between two dissociation pathways in a P-selectin adhesion bond. Proc. Natl. Acad. Sci. USA 101, 11281–11286 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Thomas, W.E., Vogel, V. & Sokurenko, E. Biophysics of catch bonds. Annu. Rev. Biophys. 37, 399–416 (2008).

    Article  CAS  PubMed  Google Scholar 

  63. Davis, D.M. & Sowinski, S. Membrane nanotubes: dynamic long-distance connections between animal cells. Nat. Rev. Mol. Cell Biol. 9, 431–436 (2008).

    Article  CAS  PubMed  Google Scholar 

  64. Bell, G.I. Models for the specific adhesion of cells to cells. Science 200, 618–627 (1978).

    Article  CAS  PubMed  Google Scholar 

  65. Sun, M. et al. Multiple membrane tethers probed by atomic force microscopy. Biophys. J. 89, 4320–4329 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Sun, M. et al. The effect of cellular cholesterol on membrane-cytoskeleton adhesion. J. Cell Sci. 120, 2223–2231 (2007).

    Article  CAS  PubMed  Google Scholar 

  67. Tulla, M. et al. TPA primes alpha2beta1 integrins for cell adhesion. FEBS Lett. 582, 3520–3524 (2008).

    Article  CAS  PubMed  Google Scholar 

  68. Ludwig, M., Dettmann, W. & Gaub, H.E. Atomic force microscope imaging contrast based on molecular recognition. Biophys. J. 72, 445–448 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Gad, M., Itoh, A. & Ikai, A. Mapping cell wall polysaccharides of living microbial cells using atomic force microscopy. Cell Biol. Int. 21, 697–706 (1997).

    Article  CAS  PubMed  Google Scholar 

  70. Hinterdorfer, P. & Dufrene, Y.F. Detection and localization of single molecular recognition events using atomic force microscopy. Nat. Methods 3, 347–355 (2006).

    Article  CAS  PubMed  Google Scholar 

  71. Grandbois, M., Dettmann, W., Benoit, M. & Gaub, H.E. Affinity imaging of red blood cells using an atomic force microscope. J. Histochem. Cytochem. 48, 719–724 (2000).

    Article  CAS  PubMed  Google Scholar 

  72. Almqvist, N. et al. Elasticity and adhesion force mapping reveals real-time clustering of growth factor receptors and associated changes in local cellular rheological properties. Biophys. J. 86, 1753–1762 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Lee, S., Mandic, J. & Van Vliet, K.J. Chemomechanical mapping of ligand-receptor binding kinetics on cells. Proc. Natl. Acad. Sci. USA 104, 9609–9614 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Dupres, V. et al. Nanoscale mapping and functional analysis of individual adhesins on living bacteria. Nat. Methods 2, 515–520 (2005).

    Article  CAS  PubMed  Google Scholar 

  75. Gilbert, Y. et al. Single-molecule force spectroscopy and imaging of the vancomycin/D-Ala-D-Ala interaction. Nano Lett. 7, 796–801 (2007).

    Article  CAS  PubMed  Google Scholar 

  76. Chtcheglova, L.A., Waschke, J., Wildling, L., Drenckhahn, D. & Hinterdorfer, P. Nano-scale dynamic recognition imaging on vascular endothelial cells. Biophys. J. 93, L11–L13 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Frisbie, C.D., Rozsnyai, L.F., Noy, A., Wrighton, M.S. & Lieber, C.M. Functional group imaging by chemical force microscopy. Science 265, 2071–2074 (1994).

    Article  CAS  PubMed  Google Scholar 

  78. Dague, E. et al. Chemical force microscopy of single live cells. Nano Lett. 7, 3026–3030 (2007).

    Article  CAS  PubMed  Google Scholar 

  79. Dague, E., Alsteens, D., Latge, J.P. & Dufrene, Y.F. High-resolution cell surface dynamics of germinating Aspergillus fumigatus conidia. Biophys. J. 94, 656–660 (2008).

    Article  CAS  PubMed  Google Scholar 

  80. Alsteens, D., Dague, E., Rouxhet, P.G., Baulard, A.R. & Dufrene, Y.F. Direct measurement of hydrophobic forces on cell surfaces using AFM. Langmuir 23, 11977–11979 (2007).

    Article  CAS  PubMed  Google Scholar 

  81. Alsteens, D. et al. Organization of the mycobacterial cell wall: a nanoscale view. Pflugers Arch. 456, 117–125 (2008).

    Article  CAS  PubMed  Google Scholar 

  82. Krieg, M. et al. Tensile forces govern germ layer organization during gastrulation. Nat. Cell Biol. 10, 429–436 (2008).

    Article  CAS  PubMed  Google Scholar 

  83. Schmidmaier, R. & Baumann, P. ANTI-ADHESION evolves to a promising therapeutic concept in oncology. Curr. Med. Chem. 15, 978–990 (2008).

    Article  CAS  PubMed  Google Scholar 

  84. Luo, B.H., Carman, C.V. & Springer, T.A. Structural basis of integrin regulation and signaling. Annu. Rev. Immunol. 25, 619–647 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Viani, M.B. et al. Probing protein-protein interactions in real time. Nat. Struct. Biol. 7, 644–647 (2000).

    Article  CAS  PubMed  Google Scholar 

  86. Humphris, A.D., Miles, M. & Hobbs, J.K. A mechanical microscope: high-speed atomic force microscopy. Appl. Phys. Lett. 86, 0341061–0341063 (2005).

    Article  CAS  Google Scholar 

  87. Yokokawa, M. et al. Fast-scanning atomic force microscopy reveals the ATP/ADP-dependent conformational changes of GroEL. EMBO J. 25, 4567–4576 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Hell, S.W. Microscopy and its focal switch. Nat. Methods 6, 24–32 (2009).

    Article  CAS  PubMed  Google Scholar 

  89. Fay, F.S. Isometric contractile properties of single isolated smooth muscle cells. Nature 265, 553–556 (1977).

    Article  CAS  PubMed  Google Scholar 

  90. Piazzesi, G. et al. Skeletal muscle performance determined by modulation of number of myosin motors rather than motor force or stroke size. Cell 131, 784–795 (2007).

    Article  CAS  PubMed  Google Scholar 

  91. Grandbois, M., Beyer, M., Rief, M., Clausen-Schaumann, H. & Gaub, H.E. How strong is a covalent bond? Science 283, 1727–1730 (1999).

    Article  CAS  PubMed  Google Scholar 

  92. Rief, M., Gautel, M., Oesterhelt, F., Fernandez, J.M. & Gaub, H.E. Reversible unfolding of individual titin immunoglobulin domains by AFM. Science 276, 1109–1112 (1997).

    Article  CAS  PubMed  Google Scholar 

  93. Oesterhelt, F. et al. Unfolding pathways of individual bacteriorhodopsins. Science 288, 143–146 (2000).

    Article  CAS  PubMed  Google Scholar 

  94. Choquet, D., Felsenfeld, D.P. & Sheetz, M.P. Extracellular matrix rigidity causes strengthening of integrin-cytoskeleton linkages. Cell 88, 39–48 (1997).

    Article  CAS  PubMed  Google Scholar 

  95. Balaban, N.Q. et al. Force and focal adhesion assembly: a close relationship studied using elastic micropatterned substrates. Nat. Cell Biol. 3, 466–472 (2001).

    Article  CAS  PubMed  Google Scholar 

  96. Vogel, V. Mechanotransduction involving multimodular proteins: converting force into biochemical signals. Annu. Rev. Biophys. Biomol. Struct. 35, 459–488 (2006).

    Article  CAS  PubMed  Google Scholar 

  97. Engler, A.J., Sen, S., Sweeney, H.L. & Discher, D.E. Matrix elasticity directs stem cell lineage specification. Cell 126, 677–689 (2006).

    Article  CAS  PubMed  Google Scholar 

  98. Vogel, V. & Sheetz, M.P. Cell fate regulation by coupling mechanical cycles to biochemical signaling pathways. Curr. Opin. Cell Biol. 21, 38–46 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Lehenkari, P.P. & Horton, M.A. Single integrin molecule adhesion forces in intact cells measured by atomic force microscopy. Biochem. Biophys. Res. Commun. 259, 645–650 (1999).

    Article  CAS  PubMed  Google Scholar 

  100. Thie, M. et al. Interactions between trophoblast and uterine epithelium: monitoring of adhesive forces. Hum. Reprod. 13, 3211–3219 (1998).

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank J. Friedrichs, M. Krieg, A. Taubenberger and A. Hyman for helpful comments. This work was supported by the European Union, the Deutsche Forschungsgemeinschaft (DFG), the Bundesministerium für Bildung und Forschung (BmbF), the National Foundation for Scientific Research (FNRS), the Université catholique de Louvain, the Région wallonne, the Federal Office for Scientific, Technical and Cultural Affairs, and the Communauté française de Belgique.

Author information

Authors and Affiliations

  1. Biotechnology Center, Technische Universität Dresden, Dresden, Germany

    Daniel J Müller & Jonne Helenius

  2. Unité de Chimie des Interfaces, Université Catholique de Louvain, Louvain-la-Neuve, Belgium

    David Alsteens & Yves F Dufrêne

Authors
  1. Daniel J Müller
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jonne Helenius
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. David Alsteens
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yves F Dufrêne
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Daniel J Müller or Yves F Dufrêne.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Müller, D., Helenius, J., Alsteens, D. et al. Force probing surfaces of living cells to molecular resolution. Nat Chem Biol 5, 383–390 (2009). https://doi.org/10.1038/nchembio.181

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nchembio.181

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing