RUI: Investigating Non-Linear Tissue Deformations Using Hydra Mouth Opening as a Quantitative in Vivo Model

Epithelial tissues are found throughout the body and exercise a variety of critical functions. Epithelial integrity is indispensable for maintaining physiological functions during development and homeostasis. Epithelial tissues withstand extreme deformations - bending, stretching, and compression - on a broad range of time and length scales.

This project creates an interdisciplinary research and education program aimed at characterizing the causes and effects of extreme deformations in epithelial tissues. A major strength lies in the originality of the experimental system: the freshwater polyp Hydra, which has been demonstrated to be a powerful in vivo biomechanical system. The PI will study Hydra mouth opening, a physiologically important process, that relies exclusively on tissue deformation wherein epithelial cells experience azimuthal strains up to 200% per cell, within tens of seconds.

Mouth opening is quick and can be visualized using epifluorescence microscopy. Thus, this is an exciting system to teach undergraduate students about dynamical systems in a hands-on teaching laboratory setting. The PI will design a 3-week mouth opening laboratory module for her Systems Biology course.

This module will provide unique hands-on exposure to tissue biomechanics. The PI will also develop a hands-on exercise on Hydra behavior for the Science for Kids program at Swarthmore College, which serves children from the neighboring town of Chester, a primarily minority community. Finally, she will build upon her track record of successfully engaging undergraduate students in her research and continue her efforts toward increasing research participation of women and other underrepresented minorities.

This study addresses fundamental questions on the role of non-linear tissue mechanics in a physiological context. Hydra mouth opening sits in the ‘Goldilocks zone’ as an in vivo biophysical system because it is simple enough for a mathematical description and complex enough to study effects of multicomponent layering, structure, and biomechanical feedback.

The PI will dissect the cellular and molecular mechanisms by which Hydra opens its mouth. It is hypothesized that mouth opening is triggered by a neuronal signal (sensation), which is propagated through the epithelium from cell-to-cell by calcium waves and/or mechanical coupling. This will be tested using in vivo fluorescence time-lapse imaging using calcium indicators, grafting experiments of normal and nerve-free Hydra strains, and physical and chemical manipulations to change cell-cell communication and mechanical properties.

The group will quantify the effect of these perturbations using existing image analysis and rheology tools. In addition the PI will determine how tissue-level constraints affect mouth opening. To study this, the PI will surgically excise different amounts of tissue and use geometrical constraints to alter head geometry.

The PI will also study the role of the extracellular matrix (ECM), which couples the epithelial cell layers via live imaging of fluorescently tagged ECM components and chemical manipulation of ECM properties. A mathematical model of the spatial and temporal dynamics of mouth opening will be developed. The PI will constrain the scaling and dependencies of the non-linear terms in the model using experimental data and extract emergent length and timescales associated with the process.

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.