All surfaces of our body, both internal and external, are covered by thin cellular layers called epithelia. Epithelia are responsible for fundamental physiological functions such as morphogenesis, compartmentalization, filtration, transport, environmental sensing and protection against pathogens. These functions are determined by the three-dimensional (3D) shape and mechanics of epithelia. However, how mechanical processes such as deformation, growth, remodeling and flow combine to enable functional 3D structures is largely unknown. Here we propose technological and conceptual advances to unveil the engineering principles that govern epithelial shape and mechanics in 3D, and to apply these principles towards the design of a new generation of biohybrid devices. By combining micropatterning, microfluidics, optogenetics and mechanical engineering we will implement an experimental platform to (1) sculpt epithelia of controlled geometry, (2) map the stress and strain tensors and luminal pressure, and (3) control these variables from the subcellular to the tissue levels. We will use this technology to engineer the elementary building blocks of epithelial morphogenesis and to reverse-engineer the shape and mechanics of intestinal organoids. We will then apply these engineering principles to build biohybrid devices based on micropatterned 3D epithelia actuated through optogenetic and mechanical control. We expect this project to enable, for the first time, full experimental access to the 3D mechanics of epithelial tissues, and to unveil the mechanical principles by which these tissues adopt and sustain their shape. Finally, our project will set the stage for a new generation of biohybrid optomechanical devices. By harnessing the capability of 3D epithelia to sense and respond to chemical and mechanical stimuli, to self-power and self-repair, and to secrete, filter, digest and transport molecules, these devices will hold unique potential to power functions in soft robots.
