BEGIN:VCALENDAR VERSION:2.0 PRODID:Icfo X-PUBLISHED-TTL:P1W BEGIN:VEVENT UID:69d8d60b06bd4 DTSTART:20220408T090000Z SEQUENCE:0 TRANSP:OPAQUE LOCATION:Auditorium and Online (Teams) SUMMARY:ICFO | VALERIA VENTURINI CLASS:PUBLIC DESCRIPTION:Living tissues are crowded and dynamic environments\, in which signalling molecules and physical forces constantly act on single cells. T o ensure correct tissue development and homeostasis\, cells function like small processors: they measure and integrate the various mechano-chemical inputs they receive from their surrounding. As an output\, cells translate this information into specific signalling pathways controlling their beha vior\, cell specification or their physical properties\, among others. %Ce lls can detect changes in chemicals and signalling molecules thanks to spe cific receptors on their surface\, and the associated signalling cascades have been well characterized. In particular\, as tissues are built\, when external stresses are applied\, or when cells rearrange and move\, single cells can undergo dynamic shape deformations. Previous studies showed that large cell deformations in confined environments control cellular contrac tility by tuning myosin II motor protein activity and can transform variou s cell types into a novel amoeboid phenotype\, termed stable-bleb. Still\, how single cells can sense shape changes and\, as a consequence\, tune my osin II activity and cell behaviour remained unknown.\nHere\, by combining planar micro-confinement assays with live cell fluorescence microscopy an d quantitative image analysis\, we performed a systematic study to charact erize the response of progenitor stem cells derived from zebrafish embryos to mechanical shape deformations. By quantifying cellular contractility l evels in various conditions and by interfering with specific signalling pa thway\, we then aimed to identify the mechano-sensitive mechanism that all ows cells to sense and respond to shape changes. We found that cells can m easure different degrees of confinement\, which accordingly defines their contractility set-point. We discovered that the nucleus\, the largest cell ular organelle\, acts as an intracellular mechano-sensor for large cell sh ape changes. Nucleus deformation induced an unfolding of the inner nuclear membrane\, which controls the activity of cytosolic phospholipase A2 (cPL A2) in the nucleus. When active\, cPLA2 triggers the release of arachidoni c acid that activates myosin II through the Rho/ROCK pathway. As a result\ , the nucleus allows single cells to accurately and dynamically sense shap e deformations and controls cellular contractility and migration plasticit y under external force load. This process\, further equips cells with an \ "escape reflex mechanism\" that allows migration away from confined enviro nments. Moreover\, the combination of inner nuclear membrane unfolding and intracellular nucleus positioning\, allows cells to sense and distinguish different shape deformations\, as anisotropic cell compression versus iso tropic swelling\, through the same mechano-sensitive pathway. Our data sup port that the nucleus establishes a functional module for cellular mechano -transduction\, enabling cells to sense and interpret different types of s hape changes and to dynamically adapt their behavior to mechanical forces in the 3D microenvironment.\n \;\nThesis Director: Dr. Stefan Wieser \ nThesis Co-Director: Dr. Verena Ruprecht DTSTAMP:20260410T105051Z END:VEVENT END:VCALENDAR