Understanding and Controlling the Cellular Forces that Coordinate Epithelial Tissue Morphogenesis

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Project Summary / Abstract Mechanical forces generated by the cellular actomyosin cytoskeleton are largely responsible for shaping sheets of epithelial cells into tissues and organs. During these morphogenetic events, the forces produced by myosin might locally promote or resist these shape changes. Our current understanding of how the structure of a myosin network influences tissue fluidity, the propensity of a tissue to remodel and flow, is lacking. In particular, it is not well understood why some epithelial cell sheets remodel and flow like fluids, while other stretch and bend like elastic solids, or how this is regulated during specific morphogenetic events. The goal of this project is to combine nanoengineering and optogenetic techniques to measure and manipulate tissues with high spatiotemporal precision to undercover the roles of actomyosin forces in tissue fluidity and morphogenesis. I will address these challenges by (1) studying myosin networks and tissue fluidity during convergent extension in Drosophila melanogaster, (2) quantitatively analyzing the forces generated by epithelial tissue sheets in vitro on nanofabricated substrates, and (3) applying these findings to tissues grown on a nanomaterial flexible substrate in an attempt to synthetically reconstitute and study three-dimensional tissue morphogenesis. These studies will improve our understanding of the mechanisms underlying how cells collectively self-organize and how perturbations in these mechanisms can lead to disease states.