Engineering a shape-changing light-actuated living tissue

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A long-standing challenge in bioengineering is to design tissues that can dynamically change their shapes on demand, for instance for regenerative purposes or for the development of biomimetic machines. For this, we propose to draw inspiration from embryonic morphogenesis when tissues undergo a series of dramatic shape changes to generate a complex organism. These are driven by spatiotemporal gradients of tension generated by the cytoskeleton and controlled by molecular switches called RhoGTPases.In turn, the activity of RhoGTPases arises from spatial patterns in the expression of genes encoding their regulators, RhoGEFs and RhoGAPs. RhoGEFs activate RhoGTPases leading to enhanced activity of myosin motors and tension, while RhoGAPs downregulate RhoGTPase activity to decrease tension. Many complex cellular morphogenetic events, such as mitotic morphogenesis, are controlled by combinations of RhoGEFs and RhoGAPs acting in different subcellularpatial locations to create the steep spatiotemporal tension gradients that lead to shape change. At the tissue scale, similar processes are at play with groups of cells coordinating their contractile and migratory behaviours to generate thelead to spatiotemporal gradients in tissue tension that drive embryonic morphogenesis.Our goal is to harness the RhoGTPase signalling pathway to create a shape-shifting living tissue that can be controlled by light, inspired by the design rules observed during embryonic morphogenesis. We will focus on two aims. First, we will design molecular actuators controlling cell mechanics based on optogenetics with one actuator increasing contractility (based on a RhoGEF) and the other decreasing contractility (based on a RhoGAP). We will then characterise their effects on cell and tissue mechanics at minute to hour time-scales. In the second aim, we will integrate these data into a computational framework that combines the theory of elasticity for tissues and evolutionary algorithms. The computational framework will suggest spatiotemporal actuation patterns to reach any desired tissue shape and we will implement these in experiments. We will focus in particular on synthetically replicating morphogenetic changes observed during embryonic development.