Transient cell stiffening triggered by magnetic nanoparticle exposure.
BACKGROUND
The interactions between nanoparticles and the biological environment have long been studied, with toxicological assays being the most common experimental route. In parallel, recent growing evidence has brought into light the important role that cell mechanics play in numerous cell biological processes. However, despite the prevalence of nanotechnology applications in biology, and in particular the increased use of magnetic nanoparticles for cell therapy and imaging, the impact of nanoparticles on the cells' mechanical properties remains poorly understood.


RESULTS
Here, we used a parallel plate rheometer to measure the impact of magnetic nanoparticles on the viscoelastic modulus G*(f) of individual cells. We show how the active uptake of nanoparticles translates into cell stiffening in a short time scale (< 30 min), at the single cell level. The cell stiffening effect is however less marked at the cell population level, when the cells are pre-labeled under a longer incubation time (2 h) with nanoparticles. 24 h later, the stiffening effect is no more present. Imaging of the nanoparticle uptake reveals almost immediate (within minutes) nanoparticle aggregation at the cell membrane, triggering early endocytosis, whereas nanoparticles are almost all confined in late or lysosomal endosomes after 2 h of uptake. Remarkably, this correlates well with the imaging of the actin cytoskeleton, with actin bundling being highly prevalent at early time points into the exposure to the nanoparticles, an effect that renormalizes after longer periods.


CONCLUSIONS
Overall, this work evidences that magnetic nanoparticle internalization, coupled to cytoskeleton remodeling, contributes to a change in the cell mechanical properties within minutes of their initial contact, leading to an increase in cell rigidity. This effect appears to be transient, reduced after hours and disappearing 24 h after the internalization has taken place.
['Perez|Jose E|JE|http://orcid.org/0000-0002-2206-0034', 'Fage|Florian|F|', 'Pereira|David|D|http://orcid.org/0000-0003-3811-8349', 'Abou-Hassan|Ali|A|http://orcid.org/0000-0002-9070-1024', 'Asnacios|Sophie|S|', 'Asnacios|Atef|A|http://orcid.org/0000-0002-3146-476X', 'Wilhelm|Claire|C|http://orcid.org/0000-0001-7024-9627']
D002462:Cell Membrane D003599:Cytoskeleton D004548:Elasticity D004705:Endocytosis D011992:Endosomes D006801:Humans D008247:Lysosomes D058185:Magnetite Nanoparticles D046529:Microscopy, Electron, Transmission D053758:Nanoparticles D036103:Nanotechnology D012212:Rheology D033081:Shear Strength D059010:Single-Cell Analysis D013314:Stress, Mechanical
Magnetic nanoparticles Parallel plate rheometer Nano-bio interface Single cell rheology