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Remote control of cellular behaviour with magnetic nanoparticles

Nature Nanotechnology volume 3, pages 139–143 (2008)Cite this article

Abstract

By binding magnetic nanoparticles to the surface of cells, it is possible to manipulate and control cell function with an external magnetic field. The technique of activating cells with magnetic nanoparticles offers a means to isolate and explore cellular mechanics and ion channel activation to gain better understanding of these processes. Here, we go beyond using this technique as an investigative tool and focus on its potential to actively control cellular functions and processes with an eye towards biological and clinical applications. In particular, we focus on applications in tissue engineering and regenerative medicine.

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Figure 1: Schematic representation of different types of nanomagnetic actuation.
Figure 2: Fluorescent images showing cell adhesion on a patterned magnetic array.
Figure 3: Tissue engineered by nanomagnetic actuation.

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References

  1. Seifritz, W. An elastic value of the protoplasm with further observations on the viscosity of the protoplasm. Brit. J. Exper. Biol. 2, 1–11 (1924).

    Google Scholar 

  2. Heilbrunn, L. V. Eine neue Methode zur Bestimmung der Viskosität lebender Protoplasten. Jahrb. Wiss. Bot. 61, 284 (1922).

    Google Scholar 

  3. Crick, F. H. C. & Hughes, A. F. W. The physical properties of cytoplasm: a study by means of the magnetic particle method. Exp. Cell Res. 1, 37–80 (1950).

    Article  Google Scholar 

  4. Valberg, P. A. & Albertini, D. F. Cytoplasmic motions, rheology and structure probed by a novel magnetic particle method. J. Cell Biol. 101, 130–140 (1985).

    Article  CAS  Google Scholar 

  5. Valberg, P. A. & Feldman, H. A. Magnetic particle motions within living cells. Measurement of cytoplasmic viscosity and motile activity. Biophys. J. 52, 551–569 (1987).

    Article  CAS  Google Scholar 

  6. Valberg, P. A. & Butler J. P. Magnetic particle motions within living cells. Physical theory and techniques. Biophys. J. 52, 537–550 (1987).

    Article  CAS  Google Scholar 

  7. Wang, N., Butler, J. P. & Ingber, D. E. Mechanotransduction across the cell surface and through the cytoskeleton. Science 260, 1124–1127 (1993).

    Article  CAS  Google Scholar 

  8. Wang N. & Ingber, D. E. Probing transmembrane mechanical coupling and cytomechanics using magnetic twisting cytometry. Biochem. Cell Biol. 73, 327–35 (1995).

    Article  CAS  Google Scholar 

  9. Ingber, D. E. Mechanical control of cyclic cAMP signalling and gene transcription through integrins. Nat. Cell Biol. 2, 666–668 (2000).

    Article  Google Scholar 

  10. Pommerenke, H. et al. Stimulation of integrin receptors using a magnetic drag force device induces intracellular free calcium response. Eur. J. Cell Biol. 70, 157–164 (1996).

    CAS  Google Scholar 

  11. Bausch, A. R., Hellerer, U., Essler, M., Aepfelbacher, M. & Sackmann, E. Rapid stiffening of integrin receptor-actin linkages in endothelial cells stimulated with thrombin: A magnetic bead microrheology study. Biophys. J. 80, 2649–2657 (2001).

    Article  CAS  Google Scholar 

  12. Bausch, A. R., Moller, W. & Sackmann, E. Measurement of local viscoelasticity and forces in living cells by magnetic tweezers. Biophys. J. 76, 573–579 (1999).

    Article  CAS  Google Scholar 

  13. Glogauer, M., Ferrier, J. & McCulloch, C. A. G. Magnetic fields applied to collagen coated beads induce stretch-activated Ca2+ flux in fibroblasts. Am. J. Physiol. 38, C1093–C1104 (1995).

    Article  Google Scholar 

  14. Glogauer, M. & Ferrier, J. A new method for application of force to cells via ferric oxide beads. Eur. J. Physiol. 435, 320–327 (1998).

    Article  CAS  Google Scholar 

  15. Pankhurst, Q. A., Connoly, J., Jones, S. K. & Dobson J. Applications of magnetic nanoparticles in biomedicine. J. Phys. D 36, R167–R181 (2003).

    Article  CAS  Google Scholar 

  16. Hughes, S., El Haj, A. J. & Dobson, J. Magnetic micro- and nanoparticle mediated activation of mechanosensitive ion channels. Med. Eng. Phys. 25, 754–762 (2005).

    Article  Google Scholar 

  17. Waigh, T. A. Microrheology of complex fluids. Rep. Prog. Phys. 68, 685–742 (2005).

    Article  Google Scholar 

  18. El Haj, A. J., Hughes, S. & Dobson, J. Manipulation of ion channels using magnetic micro- and nanoparticle cytometry. Comp. Biochem. Phys. A 134, S110 (2003).

    Google Scholar 

  19. Hughes, S., McBain, S., Dobson, J. & El Haj, A. J. Selective activation of mechanosensitive ion channels using magnetic particles. J. Roy. Soc. Interface doi:10.1098/rsif.2007.1274(2007).

  20. Howard, J. & Hudspeth, A. J. Compliance of the hair bundle associated with gating of mechanoelectrical transduction channels in the bullfrog's saccular hair cell. Neuron 1, 189–199 (1988).

    Article  CAS  Google Scholar 

  21. Walker, L. M. et al. Mechanical manipulation of bone and cartilage cells with optical tweezers. FEBS Lett. 459, 39–42 (1999).

    Article  CAS  Google Scholar 

  22. Mannix, R. J., Kumar, S., Cassiola, F., Montoya-Zavala, M. & Ingber, D. E. Nanomagnetic actuation of receptor-mediated signal transduction. Nature Nanotech. 3, 36–40 (2008).

    Article  CAS  Google Scholar 

  23. Matthews, B. D., LaVan, D. A., Overby, D. R., Karavitis, J. & Ingberg, D. E. Electromagnetic needles with submicron pole tip radii for nanomanipulation of biomolecules and living cells. Appl. Phys. Lett. 85, 2968–2970 (2004).

  24. Berry, C. C. & Curtis, A. S. G. Functionalisation of magnetic nanoparticles for applications in biomedicine. J. Phys. D 36, R198–R206 (2003).

    Article  CAS  Google Scholar 

  25. Neuberger, T., Schopf, B., Hofmann, H., Hofmann, M. & von Rechenberg, B. Superparamagnetic nanoparticles for biomedical applications: Possibilities and limitations of a new drug delivery system. J. Magn. Magn. Mater. 293, 483–496 (2005).

    Article  CAS  Google Scholar 

  26. Maheshwari, G., Brown, G., Lauffenburger, D. A., Wells, A. & Griffith, L. G. Cell adhesion and motility depend on nanoscale RGD clustering. J. Cell Sci. 113, 1677–1686 (2000).

    CAS  Google Scholar 

  27. Cavalcanti-Adam, E. A. et al. Lateral spacing of integrin ligands influences cell spreading and focal adhesion assembly. Eur. J. Cell Biol. 85, 219–224 (2006).

    Article  CAS  Google Scholar 

  28. Cavalcanti-Adam, E. A. et al. Cell spreading and focal adhesion dynamics are regulated by spacing of integrin ligands. Biophys. J. 92, 2964–2974 (2007).

    Article  CAS  Google Scholar 

  29. Polte, T. R. et al. Nanostructured magnetizable materials that switch cells between life and death. Biomaterials 28, 2783–2790 (2007).

    Article  CAS  Google Scholar 

  30. Guldberg, R. E. et al. Mechanical stimulation of tissue repair in the hydraulic bone chamber J. Bone Miner. Res. 12, 1295–302 (1997).

    Article  CAS  Google Scholar 

  31. Walker L. M., Publicover, S. J., Preston, M. R., Said Ahmed, M. A. A. & El Haj, A. J. Calcium channel activation and matrix protein up-regulation in bone cells in response to mechanical strain. J. Cell. Biochem. 79, 648–61 (2000).

    Article  CAS  Google Scholar 

  32. Wright, M., Jobanputra, P., Bavington, C., Salter, D. M. & Nuki, G. Effects of intermittent pressure-induced strain on the electrophysiology of cultured human chondrocytes: Evidence for the presence of stretch-activated membrane ion channels. Clinical Sci. 90, 61–71 (1996).

    Article  CAS  Google Scholar 

  33. Dobson, J., Keramane, A. & El Haj, A. J. Theory and applications of a magnetic force bioreactor. Eur. Cells Mater. 4 (Suppl. 2), 130–131 (2002).

    Google Scholar 

  34. Cartmell, S. H., Dobson, J., Verschueren, S. & El Haj, A. J. Development of magnetic particle techniques for long-term culture of bone cells with intermittent mechanical activation. IEEE Trans. NanoBiosci. 1, 92–97 (2002).

    Article  Google Scholar 

  35. Dobson, J., Keramane, A. & El Haj, A. J. Theory and applications of a magnetic force bioreactor. Eur. Cells Mater. 4 (Suppl. 2), 130–131 (2002).

    Google Scholar 

  36. Dobson, J., Cartmell, S. H., Keramane, A. & El Haj, A. J. A magnetic force mechanical conditioning bioreactor for tissue engineering, stem cell conditioning and dynamic in vitro screening. IEEE Trans. NanoBiosci. 5, 173–177 (2006).

    Article  Google Scholar 

  37. Hughes, S., Dobson, J. & El Haj, A. J. Magnetic targeting of mechanosensors in bone cells for tissue engineering applications. J. Biomechanics 40, S96–S104 (2007).

    Article  Google Scholar 

  38. Sura, H. S., Magnay J., Dobson J. & El Haj A. J. Gene expression in stem cells following stimulation using magnetic particle technology. Tissue Eng. 13, 1699 (2007).

    Google Scholar 

  39. Kirkham, G. R. et al. Electrophysiological responses of HMSCs and bone cells to magnetic particle tagging. Tissue Eng. 13, 1684 (2007).

    Google Scholar 

  40. Lee, I., Wang, J. H., Lee, Y. T. & Young, T. H. The differentiation of mesenchymal stem cells by mechanical stress or/and co-culture system. Biochem. Biophys. Res. Comm. 352, 147–152 (2007).

    Article  CAS  Google Scholar 

  41. Alsberg, E., Feinstein, E., Joy, M. P., Prentiss, M. & Ingber, D. E. Magnetically-guided self-assembly of fibrin matrices with ordered nano-scale structure for tissue engineering. Tissue Eng. 12, 3247–3256 (2006).

    Article  CAS  Google Scholar 

  42. Ito, A. et al. Construction and delivery of tissue-engineered human retinal pigment epithelial cell sheets, using magnetite nanoparticles and magnetic force. Tissue Eng. 11, 489–496 (2005).

    Article  CAS  Google Scholar 

  43. Ito, A., Ino, K., Kobayashi, T. & Honda, H. The effect of RGD peptide-conjugated magnetite cationic liposomes on cell growth and cell sheet harvesting. Biomaterials 26, 6185–6193 (2005).

    Article  CAS  Google Scholar 

  44. Ito, A. et al. Novel methodology for fabrication of tissue-engineered tubular constructs using magnetite nanoparticles and magnetic force. Tissue Eng. 11, 1553–1561 (2005).

    Article  CAS  Google Scholar 

  45. Pislaru, S. V. et al. Magnetic forces enable rapid endothelialization of synthetic vascular grafts. Circulation 114, I314–I318 (2006).

    Article  Google Scholar 

  46. Perea, H., Aigner, J., Hopfner, U. & Wintermantel, E. Direct magnetic tubular cell seeding: A novel approach for vascular tissue engineering. Cells Tiss. Org. 183, 156–165 (2006).

    Article  CAS  Google Scholar 

  47. Shimizu, K. et al. Effective cell-seeding technique using magnetite nanoparticles and magnetic force onto decellularized blood vessels for vascular tissue engineering. J. Biosci. Bioeng. 103, 472–478 (2007).

    Article  CAS  Google Scholar 

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Acknowledgements

The author is supported by a Royal Society Wolfson Research Merit Award and wishes to thank J. F. Collingwood and S. F. Dobson for critical readings of early versions of the manuscript.

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  1. Institute for Science & Technology in Medicine, Keele University, Thornburrow Drive, Harsthill, Stoke-on-Trent, ST9 9EZ, UK

    Jon Dobson

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Dobson, J. Remote control of cellular behaviour with magnetic nanoparticles. Nature Nanotech 3, 139–143 (2008). https://doi.org/10.1038/nnano.2008.39

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