Computational Studies of Tissue Development and Repair

Date of Award

Spring 1-1-2024

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Physics

First Advisor

O'Hern, Corey

Abstract

This thesis presents computational models of tissue mechanics to investigate physical mechanisms driving wound repair and tissue development. Recent advances in computational biology have enabled theoretical exploration of cellular dynamics, providing testable predictions for experimental validation. In the first part, a computational model of wound healing in a cellular monolayer is developed to quantify epithelial wound closure dynamics in Drosophhila embryos and larvae. The model captures the enhanced edge tension that drives wound healing and demonstrates that variations in cell membrane mechanics account for differences between developmental stages. Specifically, embryonic cell membranes behave as viscoelastic solids, while larval cell membranes behave as elastic solids. These findings suggest that plastic deformation in embryonic stages accelerates closure compared to larval stages. In the second part, a model of tissue solidification during body axis elongation in developing vertebrate embryos is presented. The computational model, constrained by Zebrafish embryo imaging data, identifies changes in cell-cell and cell-extracellular matrix (ECM) adhesion as key determinants of tissue morphology. Simulations show that increased cell-cell adhesion promotes solidification, while ECM adhesion either enhances or inhibits this process depending on matrix composition. Mutant analysis further supports a genetic basis for promoting tissue solidification through adhesion mechanics rather than motility. Hence, adhesion-driven solidification is shown to be an important mechanism of embryo morphogenesis. Together, these models provide new insights into the mechanical behaviors underlying wound repair and tissue morphogenesis, offering a quantitative framework for future investigations of tissue-scale functions.

This document is currently not available here.

Share

COinS