RUI: Hydra Whole-Body Inversion as an in Vivo Model to Study Extreme Epithelial Deformations

Epithelial cell deformations, including bending, stretching, and compression, are ubiquitous in nature and important to study from both physical and biological viewpoints to understand their roles for tissue development, maintenance, and disease. This project studies extreme tissue deformations in a novel geometry in a small freshwater animal, Hydra vulgaris. Hydra consists of a cylindrical body made out of two epithelial cell layers and has a single head-foot axis. Hydra can spontaneously invert the orientation of its body back to its normal state after having been turned inside-out. Because of Hydra’s simple anatomy and regenerative properties, this system is uniquely well-suited to study extreme epithelial deformations via experiments and mathematical modeling, and thus will deepen our understanding about how large-scale tissue deformations can be achieved and regulated. Results from this project will also inform the engineering of self-inverting cylindrical sheets, with possible applications in soft robotics. In addition, this project creates authentic research experiences for students in tissue biomechanics and provides training in quantitative skills and science communication, thus equipping the future workforce with valuable skills for careers in STEM fields and beyond. This proposal will quantify and model the extreme epithelial deformations observed during full-body inversion in Hydra vulgaris. While epithelial bending, stretching, and compression, are observed in all animals, most examples are developmental processes that affect a comparably small group of cells. This project will expand our existing knowledge on large tissue deformation. While Hydra’s inversion was first mentioned >200 years ago, only a few descriptions and drawings exist; the dynamics and mechanism of inversion are unknown. This project will quantitatively characterize Hydra inversion dynamics using live fluorescence imaging with available transgenic Hydra lines and quantify inversion time- and length scales. The researchers will measure local quantities such as cellular positions and shapes, neuronal and muscular activity via calcium imaging, and global parameters, including the positions of the foot, mouth, and major fold over time. Through genetic, physical, and chemical manipulations, the researchers will reduce the systems’ complexity and determine the “minimum ingredients” necessary for Hydra inversion to occur. The effect of these perturbations will be quantified. Finite element analysis will be used to numerically simulate a minimal system that should be capable of inversion based on experimental observation. This simulation will identify the physical mechanism required for Hydra inversion, and in doing so, provide insight into the deformation of epithelial bilayers. This project will deepen our understanding about large-scale extreme epithelial deformations and may inform new developments in active soft matter. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.