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Nanomagnetic actuation of receptor-mediated signal transduction

Abstract

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.

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Acknowledgements

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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Contributions

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 Information

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). https://doi.org/10.1038/nnano.2007.418

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