Abstract
The surrounding microenvironment limits tumour expansion, imposing a compressive stress on the tumour, but little is known how pressure propagates inside the tumour. Here we present non-destructive cell-like microsensors to locally quantify mechanical stress distribution in three-dimensional tissue. Our sensors are polyacrylamide microbeads of well-defined elasticity, size and surface coating to enable internalization within the cellular environment. By isotropically compressing multicellular spheroids (MCS), which are spherical aggregates of cells mimicking a tumour, we show that the pressure is transmitted in a non-trivial manner inside the MCS, with a pressure rise towards the core. This observed pressure profile is explained by the anisotropic arrangement of cells and our results suggest that such anisotropy alone is sufficient to explain the pressure rise inside MCS composed of a single cell type. Furthermore, such pressure distribution suggests a direct link between increased mechanical stress and previously observed lack of proliferation within the spheroids core.
Highlights
To cite this version: Monika Dolega, Morgan Delarue, François Ingremeau, Jacques Prost, Antoine Delon, et al
By isotropically compressing multicellular spheroids (MCS), which are spherical aggregates of cells mimicking a tumour, we show that the pressure is transmitted in a non-trivial manner inside the MCS, with a pressure rise towards the core
Multiple recent studies refocused on the role of mechanical cues in tissue morphogenesis and homeostasis, after pioneering works showing that biochemical signalling, and mechanical stress is indispensable for example during Drosophila gastrulation[5,6] or neural tube extension in vertebrates[7]
Summary
To cite this version: Monika Dolega, Morgan Delarue, François Ingremeau, Jacques Prost, Antoine Delon, et al. By isotropically compressing multicellular spheroids (MCS), which are spherical aggregates of cells mimicking a tumour, we show that the pressure is transmitted in a non-trivial manner inside the MCS, with a pressure rise towards the core. This observed pressure profile is explained by the anisotropic arrangement of cells and our results suggest that such anisotropy alone is sufficient to explain the pressure rise inside MCS composed of a single cell type. Despite these qualitative observations, which directly link cell behaviour with mechanical stimuli, the precise mechanisms by which mechanical forces affect crucial biological processes during development and tumorigenesis remains unknown
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