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Nanomagnetic actuation of receptor-mediated signal transduction


Complex cell behaviours are triggered by chemical ligands that bind to membrane receptors and alter intracellular signal transduction. However, future biosensors, medical devices and other microtechnologies that incorporate living cells as system components will require actuation mechanisms that are much more rapid, robust, non-invasive and easily integrated with solid-state interfaces. Here we describe a magnetic nanotechnology that activates a biochemical signalling mechanism normally switched on by binding of multivalent chemical ligands. Superparamagnetic 30-nm beads, coated with monovalent ligands and bound to transmembrane receptors, magnetize when exposed to magnetic fields, and aggregate owing to bead–bead attraction in the plane of the membrane. Associated clustering of the bound receptors acts as a nanomagnetic cellular switch that directly transduces magnetic inputs into physiological cellular outputs, with rapid system responsiveness and non-invasive dynamic control. This technique may represent a new actuator mechanism for cell-based microtechnologies and man–machine interfaces.

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Figure 1: Activation of intracellular calcium signalling by crosslinking surface-bound IgE antibodies.
Figure 2: Visualization of magnetically-induced clustering of single DNP-coated nanobeads with an electron microscope.
Figure 3: Nanomagnetic control of receptor signal transduction.
Figure 4: Dynamic responsiveness and reversibility of magnetically induced receptor signalling.


  1. Fromherz, P., Offenhausser, A., Vetter, T. & Weis, J. A neuron–silicon junction: a Retzius cell of the leech on an insulated-gate field-effect transistor. Science 252, 1290–1293 (1991).

    Article  CAS  Google Scholar 

  2. Young, T. H. & Chen, C. R. Assessment of GaN chips for culturing cerebellar granule neurons. Biomaterials 27, 3361–3367 (2006).

    Article  CAS  Google Scholar 

  3. Sutton, B. J. & Gould, H. J. The human IgE network. Nature 366, 421–428 (1993).

    Article  CAS  Google Scholar 

  4. Lu-Kuo, J. M., Joyal, D. M., Austen, K. F. & Katz, H. R. gp49B1 inhibits IgE-initiated mast cell activation through both immunoreceptor tyrosine-based inhibitory motifs, recruitment of src homology 2 domain-containing phosphatase-1, and suppression of early and late calcium mobilization. J. Biol. Chem. 274, 5791–5796 (1999).

    Article  CAS  Google Scholar 

  5. Segal, D. M., Taurog, J. D. & Metzger, H. Dimeric immunoglobulin E serves as a unit signal for mast cell degranulation. Proc. Natl Acad. Sci. USA 74, 2993–2997 (1977).

    Article  CAS  Google Scholar 

  6. Oka, T. et al. IgE alone-induced actin assembly modifies calcium signaling and degranulation in RBL-2H3 mast cells. Am. J. Physiol. Cell Physiol. 286, C256–C263 (2004).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  8. Matthews, B. D., Overby, D. R., Mannix, R. & Ingber, D. E. Cellular adaptation to mechanical stress: role of integrins, Rho, cytoskeletal tension and mechanosensitive ion channels. J. Cell Sci. 119, 508–518 (2006).

    Article  CAS  Google Scholar 

  9. Matthews, B. D. et al. Mechanical properties of individual focal adhesions probed with a magnetic microneedle. Biochem. Biophys. Res. Commun. 313, 758–764 (2004).

    Article  CAS  Google Scholar 

  10. McCreary, C. R., Dixon, S. J., Fraher, L. J., Carson, J. J. & Prato, F. S. Real-time measurement of cytosolic free calcium concentration in Jurkat cells during ELF magnetic field exposure and evaluation of the role of cell cycle. Bioelectromagnetics 27, 354–364 (2006).

    Article  CAS  Google Scholar 

  11. Glogauer, M., Ferrier, J. & McCulloch, C. A. Magnetic fields applied to collagen-coated ferric oxide beads induce stretch-activated Ca2+ flux in fibroblasts. Am. J. Physiol. 269, C1093–C1104 (1995).

    Article  CAS  Google Scholar 

  12. Meyer, C. J. et al. Mechanical control of cyclic AMP signalling and gene transcription through integrins. Nature Cell Biol. 2, 666–668 (2000).

    Article  CAS  Google Scholar 

  13. Bromley, S. K. et al. The immunological synapse. Annu. Rev. Immunol. 19, 375–396 (2001).

    Article  CAS  Google Scholar 

  14. Schreiber, A. B., Libermann, T. A., Lax, I., Yarden, Y. & Schlessinger, J. Biological role of epidermal growth factor-receptor clustering. Investigation with monoclonal anti-receptor antibodies. J. Biol. Chem. 258, 846–853 (1983).

    CAS  Google Scholar 

  15. Kim, E., Cho, K. O., Rothschild, A. & Sheng, M. Heteromultimerization and NMDA receptor-clustering activity of Chapsyn-110, a member of the PSD-95 family of proteins. Neuron 17, 103–113 (1996).

    Article  CAS  Google Scholar 

  16. Rothberg, K. G., Ying, Y. S., Kamen, B. A. & Anderson, R. G. Cholesterol controls the clustering of the glycophospholipid-anchored membrane receptor for 5-methyltetrahydrofolate. J. Cell Biol. 111, 2931–2938 (1990).

    Article  CAS  Google Scholar 

  17. Tanase, M. et al. Assembly of multicellular constructs and microarrays of cells using magnetic nanowires. Lab. Chip 5, 598–605 (2005).

    Article  CAS  Google Scholar 

  18. Koo, Y. E. et al. Brain cancer diagnosis and therapy with nanoplatforms. Adv. Drug Deliv. Rev. 58, 1556–1577 (2006).

    Article  CAS  Google Scholar 

  19. Bulte, J. W. & Kraitchman, D. L. Iron oxide MR contrast agents for molecular and cellular imaging. NMR Biomed. 17, 484–499 (2004).

    Article  CAS  Google Scholar 

  20. Grynkiewicz, G., Poenie, M. & Tsien, R. Y. A new generation of Ca2+ indicators with greatly improved fluorescence properties. J. Biol. Chem. 260, 3440–3450 (1985).

    CAS  Google Scholar 

  21. Song, J., Chen, J., Klapperich, C. M., Eng, V. & Bertozzi, C. R. Functional glass slides for in vitro evaluation of interactions between osteosarcoma TE85 cells and mineral-binding ligands. J. Mater. Chem. 14, 2643–2648 (2004).

    Article  CAS  Google Scholar 

  22. Overby, D. R., Matthews, B. D., Alsberg, E. & Ingber, D. E. Novel dynamic rheological behavior of individual focal adhesions measured within single cells using electromagnetic pulling cytometry. Acta Biomaterialia 1, 295–303 (2005).

    Article  Google Scholar 

  23. Sukharev, S. I., Sigurdson, W. J., Kung, C. & Sachs, F. Energetic and spatial parameters for gating of the bacterial large conductance mechanosensitive channel, MscL. J. Gen. Physiol. 113, 525–540 (1999).

    Article  CAS  Google Scholar 

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The authors acknowledge helpful input from J. Pendse, B. Matthews, S. Xia and R. Rogers, the use of SEM equipment at the Harvard Center for Nanoscale Systems, support from a NIH postdoctoral fellowship to S.K. (F32-NS048669), and a DARPA grant (N000140210780). The authors also wish to thank Kristin Johnson for her artwork and MagneSensors for assistance with bead magnetization measurements.

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Authors and Affiliations



R.J.M. carried out experimental work, data analysis, method development, calcium analysis and wrote the paper. S.K. was responsible for experimental design, establishing the cell system and manuscript preparation. F.C. was involved with scanning electron microscopy and data analysis, M.M-Z. with electromagnetic needle construction and experimental work, and E.F. with finite-element modelling. M.P. supervised the design of the finite-element model, and D.E.I. devised the technology concept, supervised the project, and was involved in data interpretation and manuscript preparation.

Corresponding author

Correspondence to Donald E. Ingber.

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Supplementary methods, supplementary figures S1–S3 and caption to supplementary movie (PDF 858 kb)

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Mannix, R., Kumar, S., Cassiola, F. et al. Nanomagnetic actuation of receptor-mediated signal transduction. Nature Nanotech 3, 36–40 (2008).

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