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

Autor(en): Etoc, F.
Lisse, D.
Bellaiche, Y.
Piehler, J. 
Coppey, M.
Dahan, M.
Stichwörter: Cells; Complex networks; Cytology; Molecular biology; Morphology; Nanomagnetics; Nanoparticles; Proteins; Self assembly; Signal transduction, Actin cytoskeleton; Coordinated activity; Magnetic nano-particles; Morphological changes; Signal transduction pathways; Signalling complex; Signalling pathways; Spatiotemporal patterns, Cell signaling, magnetic nanoparticle; neural Wiskott Aldrich syndrome protein; Rho guanine nucleotide binding protein, actin filament; article; cell structure; cytosol; genetic manipulation; intracellular signaling; magnetism; magnetogenetic manipulation; microenvironment; molecular dynamics; priority journal; protein binding; protein function; protein interaction; spatiotemporal analysis
Erscheinungsdatum: 2013
Herausgeber: Nature Publishing Group
Journal: Nature Nanotechnology
Volumen: 8
Ausgabe: 3
Startseite: 193
Seitenende: 198
Many cell functions rely on the coordinated activity of signalling pathways at a subcellular scale. 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 activity. We demonstrate that the nanoparticle-mediated activation of signalling pathways leads to local remodelling of the actin cytoskeleton and to morphological changes. © 2013 Macmillan Publishers Limited. All rights reserved.
ISSN: 17483387
DOI: 10.1038/nnano.2013.23
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