Enough tension will do anything in. Cells grown in a constrained environment, in a matrix or on a platform, have a bad habit of breaking due to their own strength. Though frustrating for those working in regenerative medicine, which seeks to grow replacement tissues and organs for therapy, the observation intrigued a team of bioengineers and computational scientists.
“Having worked on mechanics of hard and inactive materials it was a surprise that tissues were able to do that,” says Vivek Shenoy a professor at the University of Pennsylvania. Knowing why cells do this, and what can be done to prevent breakage, would help researchers better design tissues but, says Shenoy, the problem is deeply complex.
“Tissues are active, they remodel, heal, evolve in response to chemical and mechanical cues,” he says. “It is a challenge for a theorist to develop models that capture their complex behavior.”
In a recent PNAS Early Edition, Shenoy and co-authors, offer the first model to detail the intricate feedback effects of cells’ biochemical activity and mechanical forces.
The researchers were especially interested in the effects of myosin — a molecular motor protein that contracts when muscles fire — on tissue stability. They grew cardiac cells (or heart tissue) on minute “dogbone” shaped cantilevers and chemically influenced how tightly the myosin in the cells contracted. Cells growing in the middle of the bone stretched so intensely they could be up to thirty times longer that normal cells, the researchers report.
“Over the course of 30 hours or so, the cells pull on one another until the middle of the bone breaks. A similar process happens in each of the rings afterwards as well,” Shenoy told the University of Pennsylvania. “You can’t really hold the tissue and have it stable in this shape. It will find a way to pull, due to the myosin in the cells, and this leads to a major morphological instability.”
Measuring cellular tension a different way, researchers grew heart tissue between two flexible posts, noting how much the posts were pulled together. With some numbers on cellular strength to play with, the authors worked on building a mathematical framework for designing new shapes and materials to grow tissues.
Now, Shenoy said, “trial and error experimentation in regenerative tissue therapy can perhaps be replaced by more rational design rules guided by improved understanding of tissue mechanics.”
In the future he would like to study how tissues evolve in complex geometries, and what happens when cells of more than one type are growing together. They are already working, he says, on such questions.