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

Nat Nanotechnol. 2013 Mar;8(3):193-8. doi: 10.1038/nnano.2013.23. Epub 2013 Mar 3.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actin Cytoskeleton / chemistry*
  • Actin Cytoskeleton / metabolism
  • Actins / chemistry
  • Actins / metabolism
  • Animals
  • Cell Adhesion
  • Cell Movement
  • Magnetite Nanoparticles / chemistry*
  • Mice
  • NIH 3T3 Cells
  • Signal Transduction*
  • rac GTP-Binding Proteins / chemistry*
  • rac GTP-Binding Proteins / metabolism

Substances

  • Actins
  • Magnetite Nanoparticles
  • rac GTP-Binding Proteins