Jose E Perez1,2, Florian Fage1, David Pereira1, Ali Abou-Hassan3, Sophie Asnacios4,5, Atef Asnacios6, Claire Wilhelm7,8. 1. Laboratoire Matière et Systèmes Complexes MSC, UMR 7057, CNRS & University of Paris, 75205, Paris Cedex 13, France. 2. Institut Curie, Université PSL, Sorbonne Université, CNRS UMR 168, Laboratoire Physico Chimie Curie, 75005, Paris, France. 3. Sorbonne Université, CNRS UMR 8234, Physico-Chimie Des Électrolytes et Nanosystèmes InterfaciauX (PHENIX), 75005, Paris, France. 4. Laboratoire Matière et Systèmes Complexes MSC, UMR 7057, CNRS & University of Paris, 75205, Paris Cedex 13, France. sophie.asnacios@univ-paris-diderot.fr. 5. Faculty of Science and Engineering, UFR 925 Physics, Sorbonne Université, Paris, France. sophie.asnacios@univ-paris-diderot.fr. 6. Laboratoire Matière et Systèmes Complexes MSC, UMR 7057, CNRS & University of Paris, 75205, Paris Cedex 13, France. atef.asnacios@univ-paris-diderot.fr. 7. Laboratoire Matière et Systèmes Complexes MSC, UMR 7057, CNRS & University of Paris, 75205, Paris Cedex 13, France. claire.wilhelm@univ-paris-diderot.fr. 8. Institut Curie, Université PSL, Sorbonne Université, CNRS UMR 168, Laboratoire Physico Chimie Curie, 75005, Paris, France. claire.wilhelm@univ-paris-diderot.fr.
Abstract
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.
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.
Entities:
Keywords:
Magnetic nanoparticles; Nano-bio interface; Parallel plate rheometer; Single cell rheology
Authors: Benjamin Shapiro; Sandip Kulkarni; Aleksander Nacev; Silvia Muro; Pavel Y Stepanov; Irving N Weinberg Journal: Wiley Interdiscip Rev Nanomed Nanobiotechnol Date: 2014-11-06
Authors: Luisa H A Silva; Fernanda F Cruz; Marcelo M Morales; Daniel J Weiss; Patricia R M Rocco Journal: Stem Cell Res Ther Date: 2017-03-09 Impact factor: 6.832