Inside a cell, death often occurs like the wave at a baseball game.

What starts with two hands flung skyward prompts another, and another, until the wave has rippled far and wide across the whole stadium. This kind of a rolling surge, spurred by the activity of one or a few things, is known as a trigger wave. A new study out of the Stanford University School of Medicine has found that this phenomenon guides one of the most well-known and widespread forms of cell death: apoptosis.

It’s not the first time trigger waves have been identified in the microcosms of life. The cell cycle, a cornerstone of cell biology in which cells divide to make new cells, regulates production via trigger waves, too. So do neuronal action potentials, which allow neurons to pass signals via electrical impulse. And it likely doesn’t end there.

“This work is another example of how nature makes use of these trigger waves — things that most biologists have never heard of — over and over again,” said James Ferrell, MD, PhD, professor of chemical and systems biology and of biochemistry at Stanford. “It is a recurring theme in cell regulation. I bet we’ll start to see it in textbooks soon.”

One of the better-understood forms of cell death, apoptosis still manages to mystify scientists. “Sometimes our cells die when we really don’t want them to — say, in neurodegenerative diseases. And sometimes our cells don’t die when we really do want them to — say, in cancer,” Ferrell said. “And if we want to intervene, we need to understand how apoptosis is regulated.”

The study was published in Science Aug. 10. Ferrell is the senior author. Postdoctoral scholar Xianrui Cheng, PhD, is the lead author.

Spreads like wildfire

Trigger waves require two main elements: a positive feedback loop and a threshold — think falling dominoes. One domino collapses on another and triggers that domino to topple onto the next. The threshold is the force necessary to completely knock the tile over; a domino just shy of its threshold would teeter and rock back into a vertical position, whereas one that’s reached the threshold would fall. Trigger waves in an apoptotic cell are governed by that same phenomenon. Once cell death is initiated, by way of disease or something else, specific killer proteins in the cell, called caspases, activate. These proteins then float to other caspases and activate them; those follow suit until the entire cell has to pack it in.