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6 mai 2022: 1 événement

  • Soutenances de Thèse/HDR

    Vendredi 6 mai 14:00-16:30 - Artur Ruppel

    PhD defense : Optogenetic interrogation of intercellular propagation of force signals

    Résumé : Optogenetic interrogation of intercellular propagation of force signals
    Cell generated forces play a major role in coordinating large-scale behavior of cells, in particular during development, wound healing and cancer. Mechanical signals based on cellular force generation propagate faster than biochemical signals, but can have similar effects, especially in epithelial tissue with tight cell-cell adhesion. However, a quantitative description of the transmission chain from force generation in a sender cell, force propagation across cell-cell boundaries, and the concomitant response of receiver cells is missing due to the lack of appropriate model systems. Here we show that such a setup can be realized by combining optogenetics and micropatterning. Our minimal system are two epithelial cells on an H-pattern ("cell doublet"). After optogenetically activating RhoA, a major regulator of cell contractility, in the sender cell, we measure the mechanical response of the receiver cell by traction force and monolayer stress microscopies. In contrast to single cells on the same pattern ("cell singlet"), whose force generation after half-activation suffers from internal flows, in the cell doublet the cell boundary suppresses global flows and leads to a stable contractile situation. Force propagation and response of the receiver cell strongly depends on the actin organization in the sender cell, which we control by the aspect ratio of the H-pattern. Thus both cell-cell boundary and organization of the sender cell are essential for stimulation of the receiver cell. We quantify the active response of the receiver cell by comparing it with the passive response calculated with a mathematical model. We find that the response essentially matches the signal strength of the sender cell, and that it is the stronger the more organized the actin cytoskeleton is perpendicular to the direction of the cell-cell boundary, reminiscent of the Poisson effect in passive material. We finally show that the same effects are at work in small tissues. Our work demonstrates that cellular organization and active mechanical response of tissue is key to avoid global actin flows and to generate an elastic response that can lead to long-range mechanical signaling across the tissue.

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