According to a new study from the Stanford University School of Medicine programmed cell death or apoptosis follows a trigger and a ripple effect pattern.
Cell apoptosis, a process of programmed cell destruction that occurs in multicellular organisms, 3D illustration showing changes in cellular morphology, blebbing, cell shrinkage. Image Credit: Kateryna Kon / Shutterstock
James Ferrell, MD, Ph.D., professor of chemical and systems biology and of biochemistry at Stanford explained that cell death regulation starts with a trigger wave and this occurs in cell regulation recurrently. “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,” he added. The study titled “Apoptosis propagates through the cytoplasm as trigger waves,” on the details of apoptosis regulation is published in the journal Science this week.
Xianrui Cheng, Ph.D., a Postdoctoral scholar led this study where they found that apoptosis spreads across the cytoplasm like wildfire. The speed of movement of this wave is undeterred they noted. The researchers explain it like falling dominoes. The force necessary to trigger the cell apoptosis is all that is needed for it to spread, they noted. Once the waves start there are special proteins called caspases that are activated. These caspases activate other caspases until it has spread to the whole group of cells. Ferrell explained that it spreads “in this fashion and never slows down, never peters out.” “It doesn't get any lower in amplitude because every step of the way it's generating its own impetus by converting more inactive molecules to active molecules, until apoptosis has spread to every nook and cranny of the cell,” he said.
For their experiment Cheng and Ferrell used Xenopus laevis frog eggs as their experimental cells. Each of the eggs is a single cell. Fluid from the eggs were extracted and inserted into tiny Teflon tubes that are a few millimetres long. Then they initiated the “death signal” and started the cascade of apoptosis. They watched as the apoptosis progressed using fluorescent markers at the rate of 30 micrometers per minute. The bright green light that signified apoptosis movement progressed at a constant speed.
Cheng and Ferrell saw that when the eggs died they displayed a dark pigmentation on their surface. As the cells continued to die, the dark pigmentation spread across the cells in a curved line. They noted that the cells dying had activated caspases while the intact cells did not have activated caspases. The waves however travelled to all the cells. Ferrel said that this spread of the trigger waves could be the same way as the immune responses and viruses spread from one cell to another. He called this spread as a “recurring theme” in nature.