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IBEC Seminar: Zev Gartner
Wednesday, July 12 @ 3:00 pm–5:00 pm
Building tissues to understand how tissues build themselves
Zev Gartner, UCSF
Cells assemble into tissues and organs through an active process termed self-organization. Harnessing tissue self-organization will ultimately advance applications as diverse as disease modeling and regenerative medicine, while revealing new strategies for fighting disease. However, progress towards these applications is limited by our incomplete understanding of how the properties of tissues emerge from their cellular building blocks. I will discuss two recent projects that aim to address this knowledge gap. In a first project, we use human mammary organoids to make the remarkable observation that tissues can behave as dynamic structural ensembles. We model the ensemble using a maximum entropy framework, and demonstrate the probability distribution of tissue structures is a function of the entropy associated with cell arrangements, the energy associated with cell interfaces, and mechanical fluctuations associated with cell motility. We map these parameters back to measurable molecular and mechanical properties of cells and their microenvironment, allowing us to engineer the structural ensemble quantitatively and systematically. In a second project we use the morphogenesis of mouse intestinal villi to reveal that tuning the geometry and active mechanics of the epithelial/mesenchymal interface is sufficient to sculpt a diversity of tissue forms. In the gut, MMP and Myosin-II dependent fluidization of a contractile and adhesive sub-epithelial mesenchyme results in a dynamic monolayer of cells with a high surface tension. Minimization of surface energy results in a process we call “mesenchymal de-wetting,” which results in the formation of an array of multicellular condensates that act to pattern and fold the overlying epithelium. Manipulating the properties of the cells or the interface results in predictable changes to the pattern and shape of the folds. These studies have some important implications for tissue engineering, disease progression, and our understanding of tissue self-organization in other contexts.