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Tissues are generally subjected to external stresses, a potential stimulus for their differentiation or remodeling. While single-cell rheology has been extensively studied leading to controversial results about nonlinear response, mechanical tissue behavior under external stress is still poorly understood, in particular, the way individual cell properties translate at the tissue level. Herein, using magnetic cells we were able to form perfectly monitored cellular aggregates (magnetic molding) and to deform them under controlled applied stresses over a wide range of timescales and amplitudes (magnetic rheometer). We explore the rheology of these minimal tissue models using both standard assays (creep and oscillatory response) as well as an innovative broad spectrum solicitation coupled with inference analysis thus being able to determine in a single experiment the best rheological model. We find that multicellular aggregates exhibit a power-law response with nonlinearities leading to tissue stiffening at high stress. Moreover, we reveal the contribution of intracellular (actin network) and intercellular components (cell-cell adhesions) in this aggregate rheology.

Tissues are generally subjected to external stresses, a potential stimulus for their differentiation or remodelling. While single-cell rheology has been extensively studied, mechanical tissue behavior under external stress is still poorly known because of a lack of adapted set-ups. Herein we introduce magnetic techniques designed both to form aggregates of controlled size, shape and content (magnetic molding) and to deform them under controlled applied stresses over a wide range of timescales and amplitudes (magnetic rheometer). We explore the rheology of multicellular aggregates (F9 cells) using both standard assays (creep and oscillatory response) and an innovative broad spectrum solicitation coupled with inference analysis. We find that multicellular aggregates exhibit a power-law response with non-linearities leading to tissue stiffening at high stress. Comparing magnetic measurements on aggregates to isolated F9 cells characterization by parallel-plates rheometry, we reveal the role of cell-cell adhesions in tissue mechanics. Thanks to its versatility, the magnetic rheometer thus stands as an essential tool to investigate model tissue rheology.

International audience; In order to give insights into how anisotropic nano-objects interact with living cell membranes, and possibly self-assemble, we designed magnetic nanorods with average size around 100 nm x 1µm by assembling iron oxide nanocubes within a polymeric matrix under a magnetic field. We then explored the nano-bio interface at the cell membrane under the influence of a rotating magnetic field. We observed a complex structuration of the nanorods intertwined with the membranes. Unexpectedly, after a magnetic rotating stimulation, the resulting macrorods were able to rotate freely for multiple rotations, revealing the creation of a bio-magnetic torsion pendulum.

International audience; Multifunctional nanoparticles such as magneto‐plasmonic nanohybrids are rising theranostic agents. However, little is yet known of their fate within the cellular environment. In order to reach an understanding of their biotransformations, reliable metrics for tracking and quantification of such materials properties during their intracellular journey are needed. In this study, their long‐term (one month) intracellular fate is followed within stem‐cell spheroids used as tissue replicas. A set of magnetic (magnetization) and thermal (magnetic hyperthermia, photothermia) metrics is implemented to provide reliable insightsinto the intracellular status. It shows that biodegradation is modulated by the morphology and thickness of the gold shell. First a massive dissolution of the iron oxide core (nanoflower‐like) is observed, starting with dissociation of the multigrain structure. Second, it is demonstrated that an uninterrupted gold shell can preserve the magnetic core and properties (particularly magnetic hyperthermia). In addition to the magnetic and thermal metrics, intracellular high‐resolution chemical nanocartography evidences the gradual degradation of the magnetic cores. It also shows different transformation scenarios, from the release of small gold seeds when the magnetic core is dissolved (interesting for long‐term elimination) to the protection of the magnetic core (interesting for long‐term therapeutic applicability).

International audience; Cellular aggregates (spheroids) are widely used in biophysics and tissue engineering as model systems for biological tissues. In this Letter we propose novel methods for molding stem-cell spheroids, deforming them, and measuring their interfacial and elastic properties with a single method based on cell tagging with magnetic nanoparticles and application of a magnetic field gradient. Magnetic molding yields spheroids of unprecedented sizes (up to a few mm in diameter) and preserves tissue integrity. On subjecting these spheroids to magnetic flattening (over 150g), we observed a sizedependent elastocapillary transition with two modes of deformation: liquid-drop-like behavior for small spheroids, and elastic-sphere-like behavior for larger spheroids, followed by relaxation to a liquidlike drop.