Abstract
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.
Highlights
The remote manipulation of cellular functions through smart nanomaterials constitutes an important challenge in fundamental research, as well as in regenerative medicine
Magnetic control experiments were performed on four types of cells—human cervix adenocarcinoma HeLa cell lines and human neuroblastoma SHSy-5Y cell lines were used as two distinct “migration” models based on their size, shape and motility behavior
We observed that in magnetic nanoparticles (MNPs)-loaded PC12 cells, treatment with nerve growth factor (NGF) for 2–9 days resulted in an accumulation of MNPs in 92% of the neurite tips, with varying length, even without magnetic manipulation (Figure S2B,C)
Summary
The remote manipulation of cellular functions through smart nanomaterials constitutes an important challenge in fundamental research, as well as in regenerative medicine. Smart magnetic nanomaterials have been designed to actively respond to external magnetic fields, and to act as nano-actuators, able to mediate or convert different forms of energy into both physical and chemical cues, guiding specific cell behavior. Such nanomaterials can manipulate cellular events at distance, and at spatial and temporal scales matching their physiological dynamic range. Magnetic fields provide multiple modes to control cellular functions, via mechanical actuation, heating or by modulating protein concentrations within cells, making magnetic manipulation promising for therapeutic applications [9]
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