The Role of Cell-Cell Adhesion in Epithelial Tissue Mechanics and Morphogenesis
One of the biggest challenges in understanding how elaborate and diverse biological structures are generated in nature and in building similar structures in the lab is the gap between our knowledge of molecular-scale activities and tissue-scale behaviors. Morphogenesis, the generation of biological shape, bridges these length scales and involves significant mechanical factors. During morphogenesis, biological tissues behave as remarkable materials that can alter their properties spontaneously, respond to internal and external stimulations, and actively change shape and structure. In Drosophila embryos, for example, the germband epithelial tissue rapidly converges and extends, doubling the length of the body axis in just 30 minutes. This convergent extension process is mainly driven by local cell rearrangements, which are thought to be determined by the balance of cell-cell adhesion, mediated by junctional proteins such as E-cadherin (E-cad), and contractile tension, generated by actomyosin. Tension drives cell movements, while cell-cell adhesion plays “dual” roles by both inhibiting and promoting tissue flow. Cell-cell adhesion physically connects cells to maintain epithelial tissue cohesion, which is predicted to inhibit flow, but also organizes and transmits the forces and tensions that promote tissue flow. Therefore, it is unclear how cell-cell adhesion enacts its dual functions to impact epithelial tissue mechanical behavior and morphogenesis. In one model, increased cell-cell adhesion is predicted to slow down cell rearrangement because additional time is required to disassemble and remodel cell junctions as cells exchange neighbors. In another model, increased adhesion can alter cell shapes, which is predicted to lower the rearrangement energy barriers and result in faster cell rearrangement. To gain insight into the roles of cell-cell adhesion in epithelial tissue mechanics and morphogenesis and rule in or out specific models, we systematically modulated cell-cell adhesion in the Drosophila embryo by molecular genetics approaches to tune E-cad expression levels and studied the effects on tissue mechanical behaviors in vivo. Then, we combined live confocal imaging and quantitative image analysis to study the effects of E-cad levels on cell rearrangements and cell shapes during axis elongation. We found that E-cadherin-based cell-cell adhesion controls cell rearrangement speed and cell shapes in a biphasic manner – both high and low levels of E-cad result in cells with longer contacts with neighboring cells and faster cell rearrangements – challenging both simple models above of how adhesion influences tissue behaviors. These findings reveal surprising links between cell adhesion, cell rearrangement, and cell shape. In particular, we find that tissues comprising more elongated cells tend to have faster cell rearrangements. Interestingly, this is consistent with recent vertex model predictions that tissues with high cell shape indices are more fluid-like. Furthermore, we found that cell-cell adhesion can control cell-cell contact sizes to change cell shape by modifying its coupling to the actomyosin cytoskeleton. Particularly, we found that increased E-cadherin is associated with decreased junctional myosin II, consistent with some prior observations, suggesting that the primary role of E-cadherin in determining cell shape in this tissue is actually to regulate myosin II and tension generation, which could help explain the nontrivial effects of E-cadherin levels on cell shapes and cell rearrangement. These quantitative in vivo studies are essential to understanding the roles of cell-cell adhesion during epithelial tissue morphogenesis and development and to building and testing models of epithelial mechanics. Our work sheds light on the mechanical factors involved in embryonic development, and on how improper regulation of tissue mechanics contributes to human diseases, such as birth defects, errant wound healing and cancer metastasis. This work is also crucial for building tissues with precise shapes and structures in the lab.
The Role of Cell-Cell Adhesion in Epithelial Tissue Mechanics and Morphogenesis
Category
Poster Presentation
Description
Session: 16-01-01 National Science Foundation Posters - On Demand
ASME Paper Number: IMECE2020-24868
Session Start Time: ,
Presenting Author: Xun Wang
Presenting Author Bio: Xun Wang is a PhD candidate working as a research assistant in the Kasza Living Materials Lab in the Dept. of Mechanical Engineering, Columbia University. His research interests include biomechanics and morphogenesis. Currently, he is using transgenic techniques, live confocal imaging and quantitative image analysis to study mechanics and morphogenesis in epithelial tissues in vivo.
Authors: Xun Wang Columbia University
Christian Cupo Columbia University
Karen Kasza Columbia University