Applying Atomic Force Microscopy to Studies in Cardiac Physiology

  • Jason J. Davis
  • Trevor Powell
  • H. Allen O. Hill
Part of the Methods in Molecular Biology™ book series (MIMB, volume 242)


At the present time there exists a great deal of interest in the application of scanning probe microscopy methods to the imaging of cellular systems (1,2). It would now not be an exaggeration to state that atomic force microscopy (AFM), in particular, represents perhaps the most powerful means of structural/functional analysis at the level of a single live cell. In recent years this technology has been applied, amongst many other systems, to studies of bacterial flagella (3), erythrocytes (4), human platelets (5), endothelial cells (6), skin fibroblasts (7), plant cuticles (8), and cardiac myocytes (9). In resolution terms, perhaps the most impressive work is that of Engel et al. (10). Although not on whole cells (thereby greatly simplifying the experiment), molecular-level images of isolated cellular gap junctions, which play an important role in intracellular communication and signal transduction, have been obtained. More recently, experimental protocols have advanced to the point where it is possible to monitor, simultaneously, both cellular topography and ion channel flux (11). The ability to characterize functionally active cellular systems at a nanometre resolution under controlled fluid conditions has also been used in the monitoring of time-dependent cellular change (12,13).


Atomic Force Microscopy Scanning Probe Single Live Cell Electron Microscopy Characterization Junctional Sarcoplasmic Reticulum 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    Kasas, S., Gotzos, V., and Celio, M. R. (1993) Observation of living cells using the atomic force microscope. Biophys. J. 64, 539–544.PubMedCrossRefGoogle Scholar
  2. 2.
    Lehenkari, P. P., Charras, G. T., Nykanen, A., and Horton, M. A. (2000) Adapting atomic force microscopy for cell biology. Ultramicroscopy 82, 289–195.PubMedCrossRefGoogle Scholar
  3. 3.
    Gunning, P. A., Kirby, A. R., Parker, M. L., Gunning, A. P., and Morris, V. J. (1996) Comparative imaging of Pseudomonas putida bacterial biofilms by scanning electron microscopy and both dc contact and ac non-contact atomic force microscopy. J. Appl. Bacteriol. 81, 276–282.Google Scholar
  4. 4.
    Zhang, P., Bai, C., Huang, Y., Zhao, H., Fang, Y., Wang, N., and Li, Q (1995) Atomic force microscopy study of fine structures of the entire surface of red blood cells. Scanning Microscopy 9, 981–988.PubMedGoogle Scholar
  5. 5.
    Siedlecki, C. A. and Marchant, R. E. (1998) Atomic force microscopy for characterization of the biomaterial interface. Biomaterials 19, 441–454.PubMedCrossRefGoogle Scholar
  6. 6.
    Barbee, K. A. (1995) Changes in surface topography in endothelial cells imaged by atomic force microscopy. Biochem. Cell. Biol. 73, 501–505.PubMedCrossRefGoogle Scholar
  7. 7.
    Braet, F., Seynaeve, C., de Zanger, R., and Wisse, E. (1998) Imaging surface and submembraneous structures with the atomic force microscopy: A study on living cancer cells, fibroblasts and macrophages. J. Microscopy 190, 328–338.CrossRefGoogle Scholar
  8. 8.
    Canet, D., Rohr, R., Chamel, A., and Guillian, F. (1996) Atomic force microscopy study of isolated ivy leaf cuticles observed directly and after embedding in Epon. New Phytol. 134, 571–577.CrossRefGoogle Scholar
  9. 9.
    Davis, J. J., Hill, H. A. O., and Powell, T. (2001) High resolution scanning force microscopy of cardiac myocytes. Cell Biol. Int. 25, 1271–1277.PubMedCrossRefGoogle Scholar
  10. 10.
    Hand, G. M., Muller, D. J., Nicholson, B. J., Engel, A., and Sosinsky, G. E. (2002) Isolation and characterization of gap junctions from tissue culture cells. J. Mol. Biol. 315, 587–600.PubMedCrossRefGoogle Scholar
  11. 11.
    Schar-Zammaretti, P., Ziegler, U., Forster, I., Groscurth, P., and Spichiger-Keller, U. E. (2002) Potassium-selective atomic force microscopy on ion-releasing substrates and living cells. Anal. Chem 74, 4269–4274.PubMedCrossRefGoogle Scholar
  12. 12.
    Braunstein, D. and Spudich, A. (1994) Structure and activation dynamics of RBL-2H3 cells observed with scanning force microscopy. Biophys. J. 66, 1717–1725.PubMedCrossRefGoogle Scholar
  13. 13.
    Schoenberger, C. A. and Hoh, J. H., (1994) Slow cellular dynamics in MDCK and R5 cells monitored by time-lapse atomic force microscopy. Biophys. J. 67, 929–936.CrossRefGoogle Scholar
  14. 14.
    Schauss, S. S. and Henderson, E. R. (1997) Cell viability and probe-cell membrane interactions of XR1 glial cells imaged by atomic force microscopy. Biophys. J. 73, 1205–1214.CrossRefGoogle Scholar
  15. 15.
    Haydon, P. G., Lartius, R., Parpura, V., and Marchese-Ragona, S. P. (1996) Membrane deformation of living glial cells using atomic force microscopy. J. Microscopy 182, 114–120.CrossRefGoogle Scholar
  16. 16.
    Klebe, R. J., Bentley, K. L., and Schoen, R. C. (1981) Adhesive substrates for fibronectin. J. Cell. Physiol. 109, 481–488.PubMedCrossRefGoogle Scholar
  17. 17.
    Butt, H. J., Wolff, E. K., Gould, S. A. C., Northern, B. D., Peterson, C. M., and Hansma, P. K. (1990) Imaging cells with the atomic force microscope. J. Struct. Biol. 105, 54–61.PubMedCrossRefGoogle Scholar
  18. 18.
    Kasas, S. and Ikai, A. (1996) A method for anchoring round shaped cells for atomic force microscope imaging. Biophys. J. 68, 1678–1680.CrossRefGoogle Scholar
  19. 19.
    Gab, M. and Ikai, A. (1996) Method for immobilizing microbial cells on gel surface for dynamic AFM studies. Biophys. J. 69, 2226–2233.Google Scholar
  20. 20.
    Yamashina, S. and Shigeno, M. (1995) Application of atomic force microscopy to ultrastructural and histochemical studies of fixed and embedded cells. J. Electron Microsc. 44, 462–466.Google Scholar
  21. 21.
    Zhang, Y., Sheng, S. J., and Shao, Z. (1996) Imaging biological structures with the cryo atomic force microscope. Biophys. J. 71, 2168–2176.PubMedCrossRefGoogle Scholar
  22. 22.
    Hoh, J. H. and Schonenberger, C. A. (1994) Surface morphology and mechanical properties of MDCK monolayers by atomic force microscopy. J. Cell. Sci. 107, 1105–1114.PubMedGoogle Scholar
  23. 23.
    Domke, J., Parak, W. J., George, M., Gaub, H. E., and Radmacher, M. (1999) Mapping the mechanical pulse of single cardiomyocytes with the atomic force microscope. Eur. Biophys. J. Biophys Lett. 28, 179–186.Google Scholar
  24. 24.
    Powell, T., Noma, A., and Severs, N.J. (1998) Isolation and culture of adult cardiac myocytes, in Cell Biology: A Laboratory Handbook, 2nd ed, vol. 1 (Celis, J. E., ed). Academic Press, San Diego, CA, 1pp. 25–132Google Scholar
  25. 25.
    Severs, N. J., Slade, A. M., Powell, T., Twist, V. W., and Warren, R. L. (1982) Correlation of ultrastructure and function in calcium-tolerant myocytes isolated from the adult rat heart. J. Ultrastruct. Res. 81, 222–239.PubMedCrossRefGoogle Scholar
  26. 26.
    Powell, T., Steen, E.M., Twist, V.W., and Woolf, N. (1978) Surface characteristics of cells isolated from adult rat myocardium. J. Mol. Cell. Cardiol. 10, 287–292.PubMedCrossRefGoogle Scholar
  27. 27.
    Slade, A. M., Severs, N. J., Powell, T., Twist, V. W., and Jones, G. E. (1985) Morphometric analysis of calcium-tolerant myocytes isolated from the adult rat heart, in Advances in Myocardiology, vol. 6 (Dhalla, N. S. and Hearse D. J., eds.), Plenum Publishing Corporation, New York, pp. 3–12.Google Scholar

Copyright information

© Humana Press Inc., Totowa, NJ 2004

Authors and Affiliations

  • Jason J. Davis
    • 1
  • Trevor Powell
    • 1
  • H. Allen O. Hill
    • 2
  1. 1.Department of ChemistryUniversity of OxfordOxfordUK
  2. 2.Laboratory of PhysiologyUniversity of OxfordOxfordUK

Personalised recommendations