title: Cell-like pressure sensors reveal increase of mechanical stress towards the core of multicellular spheroids under compression.
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.
authors.affiliation: Université Grenoble Alpes, Laboratoire Interdisciplinaire de Physique, CNRS, F-38000 Grenoble, France.
authors.forename: M E
authors.initials: ME
authors.lastname: Dolega
authors.affiliation: Institut Curie, CNRS, Université P. et M. Curie, UMR168, F-75231 Paris, France.
authors.forename: M
authors.initials: M
authors.lastname: Delarue
authors.affiliation: Université Grenoble Alpes, Laboratoire Interdisciplinaire de Physique, CNRS, F-38000 Grenoble, France.
authors.forename: F
authors.initials: F
authors.lastname: Ingremeau
authors.affiliation: Institut Curie, CNRS, Université P. et M. Curie, UMR168, F-75231 Paris, France.
authors.forename: J
authors.initials: J
authors.lastname: Prost
authors.affiliation: Université Grenoble Alpes, Laboratoire Interdisciplinaire de Physique, CNRS, F-38000 Grenoble, France.
authors.forename: A
authors.initials: A
authors.lastname: Delon
authors.affiliation: Université Grenoble Alpes, Laboratoire Interdisciplinaire de Physique, CNRS, F-38000 Grenoble, France.
authors.forename: G
authors.initials: G
authors.lastname: Cappello
mesh_terms: D000180:Acrylic Resins / Q000737:chemistry; D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000502:physiology; D004548:Elasticity; D007091:Image Processing, Computer-Assisted; D051379:Mice; D018613:Microscopy, Confocal; D008863:Microspheres; D011312:Pressure; D018874:Spheroids, Cellular / Q000502:physiology*; D013312:Stress, Physiological / Q000502:physiology*; D059016:Tumor Microenvironment / Q000502:physiology*; D000099166:Polyacrylamides
chemical_list: D000180:Acrylic Resins; D000099166:Polyacrylamides