To flesh out their understanding of myosin's role in tissue stability, the researchers performed a series of physical experiments, growing heart tissue samples under various mechanical constraints while chemically altering their myosin activation.
The researchers used rapid prototyping to build "dogbone" shaped environments for the tissues to grow in. The shape, two ring-shaped wells connected by a narrow bridge, was ideal for testing mechanical properties of the cells because it forced them to stretch instead of contracting in on themselves.
The researchers also fluorescently labeled the cells so they could measure the degree to which they were stretching. They saw cells in the middle of the "bone" grow up to thirty times longer than normal, a factor that led to the tissue's ultimate demise.
"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 said. "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."
The researchers knew myosin was responsible for this instability because when they treated the tissue samples with a drug that inhibits the protein's activation, the tissues didn't break. The protein transforming growth factor beta, a protein that is a factor in scarring and tumor progression, had the opposite effect on myosin, causing the tissues to break faster.
The researchers used a different experimental set-up to test another factor that could impact myosin activity: how strongly the cells are able to pul
|Contact: Evan Lerner|
University of Pennsylvania