On October 3rd, 2017 we learned about

Dead and injured cells call for help with multiple waves of calcium signals

Owies and boo-boos are a fact of life. Even decades after we figure out how to walk, we’re still quite good at getting poked, cut or scraped with enough force to kill cells in our bodies. Fortunately, our cells have contingency plans for these events, and can spring into action around a wound to start closing it up, even without a Band-Aid! This amazing feat is something we’ve all experienced, but the exact nuts and bolts of how our cells handle it still isn’t fully understood. A new study with fluorescing proteins, high-speed cameras and super-accurate lasers has found that some of the difficulty in deciphering how our bodies heal is due to how complicated the process actually is.

A cell’s final signal

One factor that makes studying healing tricky is the speed that cells work at. In response to a wound that destroys even one cell, the surrounding tissue is “activated” by a surge in calcium ions in less than a tenth of a second. Previous studies suggested that this calcium signaling followed one of two courses. Either a dying cell releases internal fluid carrying calcium ions to nearby cells, or a signal is passed from one cell to the next at points of physical contact, which are called gap junctions. In both scenarios, the outcome would be that the healthy cells would become mobilized, moving to block up the hole left by the destroyed tissue.

So to observe how that process actually plays out, scientists had to devise a system that could track changes in calcium levels on a very tiny timescale. To make the calcium visible, scientists used fruit fly larvae that were raised with a special protein that fluoresced, or lit up, when it came in contact with calcium. So while no calcium ion would be directly observed, the ions’ path through cell proteins would glow everywhere they went. Since this happens very quickly, high-speed cameras recorded the millisecond-by-millisecond process, making it understandable to human perception. This all required an actual injury, of course, which was provided by a tiny, ultra-violet laser, capable of punching microscopic holes in a single cell at a time.

More than a single signal

The laser was fired for a single femtosecond, but that was enough to heat part of the cell, and create a cavitation bubble. The bubble is a point where pressure in a liquid suddenly drops, and then bursts, which in this case lead to non-lethal damage to the cells surrounding the laser’s target. This kicked of multiple phases of activity, starting with a burst of calcium ions pouring out of the destroyed cell. A wave of calcium increases then spread outward from the wound, mostly likely traveling between cells at gap junctions. This is all wrapped up quickly, but 45 seconds later, another wave of activity starts, spreading slower and farther than before, indicating that it’s being triggered by bigger, slower molecules. Researchers also noted that this wave only occurs when a cell has been killed, not just injured. If that weren’t enough, the next 30 minutes has even more activity. Rather than maintain the original, symmetrical flow of calcium, researchers noticed “flares” of calcium that would reach out from the injury site in a straight line, last for 10 seconds, then subside.

In the end, it seems that both models for calcium transmission were correct, but they didn’t tell the whole story on their own. The next step is to figure out what slower molecules trigger the second, bigger wave of calcium activity, as well as the intermittent “flares” into surrounding tissue. Aside from understanding how fruit fly, and human, bodies actually work, the hope is that this information will some day lead to better ways to treat injuries. We may even end up with Band-Aids that actively promote healing, even beyond the lovely placebo effect they currently provide.

Source: Cell signals that trigger wound healing are surprisingly complex, Phys.org

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