"We used a microfluidics platform that could maintain and monitor cell cultures 96 at a time," Covert said. "I was doing one at a time before that. Over a one-year period, we were able to study, with unprecedented detail, how 5,000 cells responded to signals. This took us to a totally new dimension."

The scientists put mouse fibroblast cells onto the chip and let them grow in an environmental chamber, which is mounted on an inverted microscope. The entire system, which fits on a small desktop, is computerized and provides long-term monitoring of the individual cell's response to a signal by taking pictures every few minutes.

For this study, Covert, Quake and their colleagues stimulated the cells with various concentrations of a protein that typically elicits the immune system's response to infection or cancer.

"What we found is that some cells receive the signal and activate, and some don't," said Savas Tay, PhD, a postdoctoral scholar at Stanford and at the Howard Hughes Medical Institute and co-first author of the study with graduate student Jacob Hughey. In the images, the scientists could see that the cells responded in various ways, with different timing and number of oscillations, yet their primary response, in many respects, was equal.

"Previously, we used to see the cell as a messy blob of biological material, yet there is great engineering down there," said Tay. "We needed to use mathematical modeling to understand what is going on"

"The cells were doing totally different things and we've been totally missing it," Covert said.

Added Hughey, "By observing thousands of individual cells, we were able to characterize with unprecedented detail how the cells interpret varying intensities of an external stimulus."

Source: Stanford University Medical Center