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How mechanical forces regulate tissue growth in defined 3D geometries (3D Multicell Growth)
Date du début: 1 mars 2013, Date de fin: 28 févr. 2015 PROJET  TERMINÉ 

Growth and regeneration of complex tissues are emergent phenomena resulting from the cooperative action of many cells. Besides biological signaling, the geometry of the environment plays an important role in coordinating cell behavior, and determines the shape and structure of newly formed tissue. How precisely environmental geometries are able to control cell proliferation, differentiation and extracellular matrix deposition remains a challenge. In this project, a novel in vitro model platform will be developed to determine the interplay of external geometry and cell generated mechanical forces to direct multicellular tissue formation in 3D scaffold geometries. This approach integrates a quantitative growth assay using osteoblasts as cell model with leading-edge techniques for 3D substrate fabrication and molecular strain sensors. Matrix strains and stress fluctuations will be measured under systematically varying geometrical conditions while simultaneously monitoring proliferation and extracellular matrix production in order to test how mechanical parameters and cell behavior are correlated. The contribution of different mechanobiological mechanisms by which cells react to mechanical signals will be identified by selectively inhibiting cellular adhesion, contractility, and mechanotransduction pathways. The results of this project will not only shed light on the mechanisms behind osteoblast tissue deposition and bone remodeling, but also on the role of geometry and mechanics for tissue growth and regeneration in general. The Vogel lab at ETH Zurich has developed world leading techniques for molecular imaging of extracellular matrix strains, and for the fabrication of controlled cell environments. The combination of these techniques with the skills and expertise of the candidate will improve his potential to achieve professional maturity and provide a unique opportunity to increase the competitiveness of European science in the field of multicellular bioengineering.