Post-doctoral fellow Roland Kaunas, now an assistant professor of biomedical engineering at Texas A&M University, with the help of UCSD laboratory assistant Phu Nguyen, found that unstretched cells or cells that were stretched only 1 percent of their length contained actin fibers with no directional orientation. However, as they increased the rhythmic stretching from 3 percent of a cell's length to 10 percent, stretch fibers became increasingly oriented perpendicular to the stretching direction.

In the most significant finding in the PNAS article, which was made available online Oct. 24, Chien's group reported that when an intracellular protein called Rho was chemically inhibited, stress fibers grew in the "wrong" direction; they grew parallel rather than perpendicular to the direction of cell stretching. Without Rho, the cells lost their ability to orient stress fibers properly. "Rho is a very important molecule," said Chien. "It works in response to, and in concert with, physical stretching to generate the healthy alignment of stress fibers." Indeed, when Chien's group used a genetic technique to increase the activity of Rho, those cells grew stress fibers in the healthy direction at a lower threshold of stretching.

"Until now, it has not been shown that there is an equivalence and cooperation between mechanical and biochemical stimuli to regulate the proper orientation of these stress fibers," said Kaunas. "Indeed, we found that the stress fibers oriented in such a way to control their level of stress not too little and not too much."

Chien and Kaunas collaborated with UCSD research scientist Shunichi Usami, who contributed to the design of the miniature workout chambers. Silicone rubber membranes inside the chambers were coated with a protein that allowed the endothelial
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Contact: Rex Graham
ragraham@ucsd.edu
858-822-3075
University of California - San Diego
24-Oct-2005