As with the previous set of experiments, naturally growing tissues would pull themselves apart in a matter of hours. But by altering the stiffness of the posts, or by increasing the amount of collagen, a key component of the extracellular matrix that holds the tissue together and determines how hard it can pull, the researchers found that they could make the tissues last longer.
"In the control set-up with the amount of collagen you would normally see in the heart, we see this bridge of tissue pull itself apart by day three," Shenoy said, "If you increase the collagen, or make the posts less stiff, you see that the tissues becomes more stable."
"The myosin in the cells are pulling on actin filaments attached to the inside of the cells' membranes, but if you anchor the cells, the contraction rate will decrease, eventually going to zero. That's isometric tension at work," he said.
With these factors quantified, Shenoy and his colleagues were able to build a more comprehensive model of mechanical failure when cells pull on one another. Their model was able to solve a long-standing conundrum found in previous models: all of the molecular components of a cell suggest that it should act like a "strain-hardening" material, something that gets tougher when pulled upon.
"These previous models were passive, they looked at all of the components of the cells but didn't take into account the dynamic role that myosin plays," Shenoy said. "Now that we have these three mechanical factors in our model, the cell-to-cell contacts, the role the extracellular matrix plays, and now the active myosin element, we can truly understand the sources of instability."
Their model enabled the researchers to generate a phase di
|Contact: Evan Lerner|
University of Pennsylvania