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Subcellular control of Rac-GTPase signalling by magnetogenetic manipulation inside living cells

Nature Nanotechnology volume 8, pages 193–198 (2013)Cite this article

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Abstract

Many cell functions rely on the coordinated activity of signalling pathways at a subcellular scale1,2. However, there are few tools capable of probing and perturbing signalling networks with a spatial resolution matching the intracellular dimensions of their activity patterns. Here we present a generic magnetogenetic approach based on the self-assembly of signalling complexes on the surface of functionalized magnetic nanoparticles inside living cells. The nanoparticles act as nanoscopic hot spots that can be displaced by magnetic forces and trigger signal transduction pathways that bring about a cell response. We applied this strategy to Rho-GTPases, a set of molecular switches known to regulate cell morphology via complex spatiotemporal patterns of activity3,4. We demonstrate that the nanoparticle-mediated activation of signalling pathways leads to local remodelling of the actin cytoskeleton and to morphological changes.

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Figure 1: Intracellular manipulation of fMNPs and protein functionalization schemes.
Figure 2: Cdc42–MNPs behave as cytosolic signalling patches.
Figure 3: Remote control of Rho-GTPase signalling at the plasma membrane.
Figure 4: Rac1-mediated actin polymerization is context-dependent.

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Acknowledgements

The authors thank B. Mueller and M. Warntjen for their contributions to the initial stage of this project, O. Chen and M. Bawendi for useful discussions on magnetic nanoparticles, D. Lévy for his help with electron microscopy and P.F. Lenne for a critical reading of the manuscript. This work was supported by the Human Frontier Science Program (grant no. RGP0005/2007).

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Author notes

  1. F. Etoc, M. Coppey & M. Dahan

    Present address: Present address: Laboratoire Physico-chimie Curie, Unité Mixte de Recherche 168, Centre de Recherche, Institut Curie, CNRS, et Université Pierre et Marie Curie-Paris 6, Paris, France,

Authors and Affiliations

  1. Département de Physique et Institut de Biologie, Laboratoire Kastler Brossel, CNRS UMR 8552, Ecole normale supérieure, Université Pierre et Marie Curie-Paris 6, Paris, France

    F. Etoc, M. Coppey & M. Dahan

  2. Department of Biology, University of Osnabrück, 49076 Osnabrück, Germany

    D. Lisse & J. Piehler

  3. Division and Morphogenesis Team, Polarity, Institut Curie, CNRS UMR 3215, INSERM U934, Paris, France

    Y. Bellaiche

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Contributions

F.E., D.L.,Y.B., J.P., M.C. and M.D. conceived the project and designed the experiments. F.E., D.L. and M.C. acquired and analysed the data. F.E., J.P., M.C. and M.D. wrote the manuscript.

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Correspondence to J. Piehler or M. Dahan.

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The authors declare no competing financial interests.

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Etoc, F., Lisse, D., Bellaiche, Y. et al. Subcellular control of Rac-GTPase signalling by magnetogenetic manipulation inside living cells. Nature Nanotech 8, 193–198 (2013). https://doi.org/10.1038/nnano.2013.23

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