Parallelized manipulation of adherent living cells by magnetic nanoparticles-mediated forces

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 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.

Self-Assembled Permanent Micro-Magnets in a Polymer-Based Microfluidic Device for Magnetic Cell Sorting

“…The attractive force acting on the probe, measured by the cantilever deflection, is linked to the magnetic force. Contact forces ranging from 0.5 to 2 nN were measured ( Figure 4 a), and these values are in agreement with the data found in the literature for microscale soft magnetic sources [ 26 , 27 , 28 ] and hard magnetic structures [ 29 ]. The mapping of the magnetic attraction, performed at a distance of 500 nm from the surface, highlights that the maximum force is localized above the micro-magnet ( Figure 4 a, inset).…”

Live-cell micromanipulation of a genomic locus reveals interphase chromatin mechanics

“…S3). Cells were imaged on a coverglass with custommade microfabricated pillars 26,27 , which behave as local magnets only when subjected to an external magnetizing field (Fig. S4).…”

“…Microarrays of magnetic pillars on glass coverslips were produced as described in Bongaerts et al 27 and Toraille, Aizel et al 26 , using conventional microfabrication techniques. Briefly, 10µm of permalloy (nickel-iron alloy) were deposited by electroplating on a glass coverslip, over 100x100µm square regions obtained by photolithography and arranged every 270µm on a grid pattern (Fig.…”

“…Each microarray coverglass was mounted in a custom-made aluminum holder designed to allow the reproducible placement and removal of an external double-magnet while performing imaging 27 . The double magnet (AIP20X20X20, Magnetiques.fr) was measured to produce a uniform 100mT magnetic field, which saturates the micropillars when placed onto the holder (the micropillars saturate at 50~70 mT and show a very low remanence 26 ).…”

Directional control of neurite outgrowth: emerging technologies for Parkinson's disease using magnetic nanoparticles and magnetic field gradients

“…Therefore, it is considered that other approaches to generating directional cues could help achieve more complete reinnervation. One potential approach to generating topological gradients and directional cues is through the use of MNPs guided by magnetic fields [6,8,9,12,13]. MNPs are a suitable candidate for applying mechanical forces to neuronal cells, being widely used in biomedicine settings, such uses as MRI contrasts [14–16], and are commercially available, with previously demonstrated biological safety.…”