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Rosse, C.

Publications and source records attributed to Rosse, C..

4 recordsLinked to original sources

A principal-stress rule for cell division in epithelia

Dense active materials, from cellular tissues to jammed and glassy systems, must continuously relieve internal mechanical stress to remain structurally stable as they are driven far from equilibrium. In epithelial tissues, this relief occurs through cell division, yet what sets the geometry of this structural remodeling event has, for over a century, been attributed to a purely geometric principle: Hertwigs rule, whereby cells divide along their long axis. We show that as epithelial tissues densify and cell shape anisotropy collapses, this geometric rule is superseded by a mechanical one in which dense epithelia relieve anisotropic stress by cells dividing along their principal axis, independent of the tissues isotropic stress state. Using direct force measurement and stress inference, we show that stress orientation, rather than cell shape, governs the axis of cell division across mechanically distinct systems, from fluid-like to jammed monolayers and structurally heterogeneous organoids, remaining predictive precisely where the classical geometric rule fails. This stress-oriented remodeling is reciprocally coupled to the materials mechanical state: anisotropic stress accelerates the underlying remodeling rate, while each remodeling event locally dissipates the stress that triggered it, closing a negative feedback loop. This "principal-stress rule" recasts epithelial cell division as a stress-relief mechanism intrinsic to dense active matter, providing a general mechanical framework linking internal stress, structural remodeling, and homeostasis in living materials.

biophysics↗

Force transmission is a master regulator of mechanical cell competition

Cell competition is a tissue surveillance mechanism for eliminating unwanted cells and as such is indispensable in development, infection and tumorigenesis. Although different biochemical mechanisms are proposed, due to the dearth of direct force measurements, how mechanical forces determine the competition outcome remains unclear. Here, using ex vivo tissues and different cell lines, we have discovered an unknown form of cell competition that is regulated by differences in force transmission capabilities, favoring cell types with stronger intercellular adhesion. Direct force measurements reveal increased mechanical activity at the interface of the two competing cell types in the form of large stress fluctuations which can lead to upward forces and cell elimination. We show how a winning cell type endowed with a stronger intercellular adhesion exhibits a higher resistance to elimination while benefiting from efficient force transmission to neighboring cells. This cell elimination mechanism could have broad implications of keeping strong force transmission ability for maintaining tissue boundaries and cell invasion pathology.

biophysics↗

A new approach to measure forces at junction vertices in an epithelium

The mechanical properties of cell-cell junctions are critical for the stability of an epithelium. Cell-cell junction ablation experiments are classically used as a readout for junctional mechanics. However, without the knowledge of the viscoelastic properties of the microenvironment of the ablated junction, tensile junctional forces cannot be measured. Here we combine laser ablation with intracellular microrheology and develop a model to measure tensile forces exerted on cell-cell junctions. We show that the overexpression of the proto-oncogene atypical Protein Kinase C iota (aPKCi) in a single cell within a normal epithelium induces a gradient of junctional tension with neighbouring cells. Our method allows us to demonstrate that junctions contacting the aPKCi-overexpressing cell display a mechanical asymmetry which correlates with the levels of E-cadherin and P-MLC2. Measuring intracellular viscoelasticity is crucial for accurate measurements of cell-cell junction mechanics in the context of development or cancer research. TeaserWe combine cytoplasmic and junctional mechanics to detect asymmetry in forces exerted on cell-cell junctions.

cell biology↗

A new analytical pipeline for the study of the onset of mammary gland oncogenesis based on mammary organoid transplantation and organ clearing

Metastasis formation is a multi-step process starting from the dissemination of transformed carcinomatous cells from the primary tumor and could occur at a very early stage of oncogenesis, before primary tumor detection. The adult mammary gland provides a unique model to investigate epithelial cell dissemination processes. Tissue clearing techniques allow imaging samples of large volume. uDSICO clearing, one of the latest tissue clearing technique developed, provides optical imaging of whole organ due to organ clearing and tissue size reduction. We wanted to take advantage of this technique to study rare events occurring in vivo. Here, we have established a new analytical pipeline exploiting the regenerative properties of the mammary epithelium following orthotropic transplantation of organoids together with the uDISCO organ size reduction and clearing method to study early cell dissemination in the mammary gland. As proof of concept, we analyzed the localization of epithelial cells overexpressing the oncogenic protein atypical protein kinase C iota (aPKCi+) in the normal mammary gland and we were able to visualize epithelial aPKCi+ cells, surrounded by normal epithelial cells, escaping from the normal mammary epithelium and disseminating into the surrounding stroma.

cell biology↗