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

F. Etoc, D. Lisse, Y. Bellaiche, J. Piehler, M. Coppey and M. Dahan

Many cell functions rely on the coordinated activity of signaling pathways at a subcellular scale. However, there are few tools capable of probing and perturbing signaling networks with a spatial resolution matching the intracellular dimensions of their activity patterns. Here we present a generic magneto genetic approach based on the self-assembly of signaling 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 signaling pathways leads to local remodelling of the actin cytoskeleton and to morphological changes.