ARLINGTON , Va. , June 22, 2005 – Biomedical engineers have captured on video for the first time a wave of chemical signals radiating from the point of contact when something pokes or pulls on a human cell. This cascade of signals could be useful in diagnosing different forms of cancer.

In the April issue of Nature, researchers at the University of California, San Diego, (UCSD) describe their novel molecular reporter system that can capture and record the activity of a key protein called Src.

UCSD Video Stream

The researchers attached small, sticky beads to cells and gently tugged the beads back and forth with lasers acting like invisible, miniature tweezers. The cells, in response, sent biochemical signals in the direction opposite each tug, like waves spreading from a pebble tossed into a pond. A video camera attached to a specially equipped microscope used fluorescence resonance energy transfer to record the dynamic movement of biochemical signals in the opposite direction, forming a signature pattern of fluorescent light.

"We had no idea what to expect," said Peter Yingxiao Wang, lead author of the paper and a post-doctoral researcher in UCSD's Jacobs School of Engineering. "The first time we saw these incredible waves spreading across the cells I just said 'This is amazing.' We expected to see a signal where the tweezers were pulling the beads, but we did not envision such a directional wave propagating away from the beads."

Src is one of a large group of enzymes called kinases that attach a phosphate molecule to target proteins in the cell. This attachment reaction typically activates the target protein to perform vital metabolic functions. Many diseases can result when either phosphate molecules fail to properly attach to certain proteins, or when the kinase becomes too active or too inactive. Src has been shown to play a key role in cell growth and development, as well as cancer, atherosclerosis, and many other diseases.

The researchers also showed that actin filaments and microtubules, structural elements that traverse cells like the ribs of an umbrella, could function as conduits through which the biochemical signals can spread. When researchers disrupted either actin filaments or microtubules in test cells, the chemical activation signal no longer spread across the cell. These results suggest that the activation of Src traverses these filamentous structures.

"This study amounts to a proof of principle that if we can visualize the activation of one kinase, we can do the same for many others using the same approach," said Shu Chien, M.D., Ph.D., the senior author and a professor of bioengineering and medicine and director of the Whitaker Institute of Biomedical Engineering at UCSD. Because Src activity is abnormally high in certain cancers, "we think that our ability to measure Src activity with this new visualization technique would be useful as a diagnostic test for many cancers," said Chien.

This work was supported in part by The Whitaker Foundation.