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Bongaerts M., Aizel K., Secret E., Jan A., Nahar T., Raudzus F., Neumann S., Telling N., Heumann R., Siaugue J.-M., Ménager C., Fresnais J., Villard C., El Haj A., Piehler J., Gates M.A. and Coppey M. (2020).
Parallelized manipulation of adherent living cells by magnetic nanoparticles-mediated forces.
Int. J. Mol. Sci. 21(18): 6560
doi: 10.3390/ijms21186560

The remote actuation of cellular processes such as migration or neuronal outgrowth is a challenge for future therapeutic applications in regenerative medicine. Among the different methods that have been proposed, the use of magnetic nanoparticles appears to be promising, since magnetic fields can act at a distance without interactions with the surrounding biological system. To control biological processes at a subcellular spatial resolution, magnetic nanoparticles can be used either to induce biochemical reactions locally or to apply forces on different elements of the cell. Here, we show that cell migration and neurite outgrowth can be directed by the forces produced by a switchable parallelized array of micro-magnetic pillars, following the passive uptake of nanoparticles. Using live cell imaging, we first demonstrate that adherent cell migration can be biased toward magnetic pillars and that cells can be reversibly trapped onto these pillars. Second, using differentiated neuronal cells we were able to induce events of neurite outgrowth in the direction of the pillars without impending cell viability. Our results show that the range of forces applied needs to be adapted precisely to the cellular process under consideration. We propose that cellular actuation is the result of the force on the plasma membrane caused by magnetically filled endo-compartments, which exert a pulling force on the cell periphery.