Dynamic Tension Model Sheds Light on Epithelial Tissue Architecture

Epithelial cells are the living building blocks of tissues and organs. They form multicellular sheets that cover internal and external surfaces in living organisms. How cells move within epithelial tissues to shape living organisms has been a question of longstanding interest in developmental biology. Carnegie Mellon University researchers have recently made significant strides in answering this question using biophysical models and simulations.

"At the level of an individual cell, it has been shown that there is feedback between contraction and an increase in tension," said Fernanda Pérez-Verdugo, a postdoctoral researcher in the Department of Physics. "We wanted to explore what cellular structures could arise if we applied similar rules to an entire tissue."

Pérez-Verdugo and Shiladitya Banerjee, associate professor of physics, created a computational model that shows epithelial cells create multicellular rosettes, tight-knit groups of cells, through a combination of strain-dependent tension remodeling and mechanical memory dissipation.

"One of the key ideas that emerged out of this work is that there is continuous tension remodeling going on in epithelial tissues, with cells being stretched or compressed as they are trying to move around within the tissue," Banerjee said. "Cells are under constant pulling and pushing, the tension is continuously remodeling to accommodate these deformations. If you think about tissues as materials, they can adjust their mechanical properties continuously."

Building on their previous research, Pérez-Verdugo and Banerjee created a complex computational program that included cellular motion, mechanics, and topological transitions in epithelial tissues.

"An exciting result of our research is that tension remodeling, at the cellular level, controls tissue fluidity. In its absence, cells don't move too much; for high remodeling, cells move a lot." Pérez-Verdugo said. "This is the first work in which the fluid state of the tissue can be understood in terms of cellular level mechanisms."

Pérez-Verdugo and Banerjee said that knowing how epithelial cells form multicellular rosettes could be helpful for biologists investigating embryonic development. As an example, it has been shown that some fruit flies that do not develop properly have a long presence of rosettes during embryonic development. Since they now have a physical basis for the formation of multicellular structures, researchers in the future might be able to control the formation of these structures.

Pérez-Verdugo and Banerjee plan to adapt the computational program to further investigate the physics behind embryonic development and morphogenesis.

"We are trying to understand the implications of these tissue architectures for the mechanics of the tissue itself and to apply this model to specific developmental contexts," Banerjee said.

Pérez-Verdugo and Banerjee collaborated on "Tension Remodeling Regulates Topological Transitions in Epithelial Tissues," published in Physical Review X Life and featured in the American Physical Society Physics Magazine. The research was funded by the National Institutes of Health Grant No. NIH R35-GM143042.