All-in-one rheology of multicellular aggregates

Abstract 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.