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Researchers at UCSD and UC Irvine have captured on video for the first time chemical signals that traverse human cells in response to tiny mechanical jabs, like waves spreading from pebbles tossed into a pond. The scientists released the videos and technical details that explain how the visualization effect was created as part of a paper published in the April 21 issue of Nature.
The researchers working at the UCSD Jacobs School of Engineering's Department of Bioengineering developed a novel molecular "reporter" system, which allowed the dynamic visualization of the activation of an important protein called Src. Peter Yingxiao Wang, lead author of the paper and a post-doctoral researcher in UCSD's Jacobs School of Engineering spent two years designing the reporter molecules to light up selectively only when Src was activated, and not other proteins.
Wang and his co-workers first demonstrated that the novel system was effective in visualizing Src activation in response to a known chemical stimulant, epidermal growth factor. Next, they studied the effect of mechanical stimuli on Src activation. Using technology developed at the Beckman Laser Institute at UC Irvine by its founding director Michael Berns, Wang and Elliott Botvinick, a postdoctoral researcher at UCSD Department of Bioengineering and the Beckman Laser Institute at UC Irvine, attached small, sticky beads to cells and gently tugged the beads to and fro with laser power acting as invisible "tweezers." As the laser tweezers moved the beads in one direction, a video camera attached to a specially equipped microscope recorded the dynamic movement of biochemical signals in the opposite direction in the form of a signature pattern of fluorescent light. The fine spatial and temporal resolution was made possible by a technology called fluorescence resonance energy transfer.
"We had no idea what to expect," said Wang. "The first time we saw these incredible waves spreading across the cells I just said 'Whoa, 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." Wang worked on this project under the joint advisorship of Shu Chien, a professor of bioengineering and medicine and director of the Whitaker Institute of Biomedical Engineering at UCSD, and Roger Y. Tsien, professor of pharmacology, chemistry, and biochemistry and investigator with the Howard Hughes Medical Institute at UCSD.