Exploring the Role of Endothelial-epithelial Mechanical Interactions in Shaping Mini-organs

Cellular forces and their interactions with the extracellular environment play a crucial role in the shaping of tissues and organs (called morphogenesis). In my PhD I will explore the role of mechanical interactions between epithelial and endothelial cells for the complex 3D organization of vascularized mini-organs. In order to do, I will create minimal, yet physiologically relevant 3D in vitro co-culture models of epithelial and endothelial cells and their extracellular matrix. In these models, I will among others manipulate the expression of adhesion receptors, their extracellular ligands, molecules that are involved in cellular force exertion (through their effect on cytoskeletal organization), using genetic engineering tools. I will quantify their direct effect on cell-cell and cell-matrix forces and multicellular organization, using 3D live cell optical imaging, FRET-based molecular force sensors and Traction Force Microscopy (TFM). While my work will be mainly focused on in vitro experimentation, I will also have access to in vivo data on the role of vascularization in mini-organ morphogenesis, so that in vitro and in vivo models can mutually influence each other for hypothesis testing. Finally, my in vitro data will serve as input for computational models of multicellular organization, which can generate additional insight in the role of cellular forces. The work is part of a recently approved iBOF project called “Synthetic organogenesis: the role of blood vessels in orchestrating the development and morphogenesis of ectopic miniorgans” and will be in close collaboration with Georg Halder (KU Leuven) and Leo van Grunsven (VUB).