Cell signals that trigger wound healing are surprisingly complex

From the Summer 2018 edition of Vanderbilt Medicine Magazine

In a sharp and pointy world, wound healing is a critical and marvelous process.

Despite a tremendous amount of scientific study, many outstanding mysteries still surround the way in which cells in living tissue respond to and repair physical damage.

One prominent mystery is exactly how wound-healing is triggered. A better understanding of this process is essential for developing new and improved methods for treating wounds of all types.

Using an ultrafast, ultraprecise laser, a team of physicists and biologists at Vanderbilt University has taken an important step toward understanding the nature of these trigger signals. Their new insights are described in a paper titled “Multiple mechanisms drive calcium signal dynamics around laser induced epithelial wounds” published in October 2017 by the Biophysical Journal.

Previous research had determined that calcium ions play a key role in wound response. That is not surprising, because calcium signaling has an impact on nearly every aspect of cellular life. So, the researchers — headed by Professor of Physics and Biological Sciences Shane Hutson and Associate Professor of Cell and Developmental Biology and Chancellor’s Fellow Andrea Page-McCaw—targeted cells on the back of fruit fly pupae that expressed a protein that fluoresces in the presence of calcium ions. This allowed them to track changes in calcium ion concentrations in the cells around wounds in living tissue (as opposed to the cell cultures used in many previous wound response studies) and to do so with an unprecedented, millisecond precision.

The team created microscopic wounds in the pupae’s epithelial layer using a laser that can be focused down to a point small enough to punch microscopic holes in individual cells (less than a millionth of a meter). The laser’s precision allowed them to create repeatable and controllable wounds. They found that even the briefest of pulses in the nanosecond to femtosecond range produced a microscopic explosion called a cavitation bubble powerful enough to damage nearby cells.

“As a result, the damage the laser pulses produce is quite similar to a puncture wound surrounded by a crush wound — blunt force trauma in forensic terms — so our observations should apply to most common wounds,” said first author Erica Shannon, a doctoral student in developmental biology.