The earliest steps of development are characterized by cellular reorganization and differentiation within a 3D microenvironment. This 3D context allows for a complex interplay between biochemical and mechanical signals, and governs important cellular rearrangements leading to morphogenesis. In vitro approaches have attempted to recapitulate key features of these processes, and it has become possible to generate an increasing variety of self-organizing tissue constructs termed ‘organoids’. While important aspects of the 3D in vivo organization have been recreated using organoids, such studies have been exclusively performed in ill-defined matrices whose properties cannot be controlled. As such, the uncharacterized interactions between cells and this extracellular matrix have proven to be a major challenge to understanding the underlying regulatory mechanisms governing morphogenesis. In this talk, I will highlight our recent efforts to employ tunable synthetic microenvironments to disentangle the contributions of biochemical and, in particular, mechanical effectors in specifying intestinal stem cell fate and self-organization.

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Bio

Professor Matthias Lutolf is Head of the Laboratory of Stem Cell Bioengineering at Ecole Polytechnique Fédérale de Lausanne (EPFL), Switzerland. His highly innovative and cross-disciplinary research program is focused on the development of bio- and tissue-engineering strategies for improving organoid culture and enabling its translation to real-life applications.