For unwanted cells, death comes in waves


Study finds a very neat intersection of physics and biology. Paul Biegler reports.


A trigger wave bringing death to frog cells.
A trigger wave bringing death to frog cells.
Cheng et al

It may come as a shock to learn that 50 billion of your body’s cells met their end yesterday, at their own hand no less. It would, however, be wise to get used to it because it will happen today and again tomorrow. It is called apoptosis and is, in fact, essential for survival.

Each day the body produces billions of excess cells that are slated for removal. In early life, some of that is just healthy embryology, such as the creation of fingers in the foetus by the carving of web spaces in its paddle-shaped hands – think of a sculptor building a clay model only to cleave away the surplus to reveal an exquisite Renaissance rendering of David.

But apoptosis also keeps aberrant growth at bay, for example, by pruning back misdirected neurons or imploding immune cells that wrongly turn on the self. It is a delicate balance. Too little apoptosis and cells would become cancerous, too much and the organ withers.

Our understanding of how the process occurs just got a boost from a study by Xianrui Cheng and James Ferrell at the Stanford University School of Medicine, California, US.

The researchers were faced with two candidate mechanisms for how death propagates through cells.

The first was a random process of diffusion – a path that can be likened to an animal foraging through forest, which gradually loses energy and slows with time. The second candidate was a trigger wave, the speed of which is maintained or increased by virtue of positive feedback – much like a wildfire fuelled by tinder-dry bush.

To deduce which mechanism was in effect, the team enlisted the services of a fearsome aquatic creature called the African clawed frog (Xenopus laevis), whose hind foot appendages and predatory nature make it a very poor aquarium mate for small fish.

The frog’s main claim to fame, however, is the relative enormity of its egg cells, which, at a little over a millimetre, make them ideal to study. Cheng and Ferrell extracted the contents of said cells and placed them in fine microtubules with the aim of monitoring the spread of apoptosis through the solution.

This was done with the aid of a green fluorescent marker that registered the action of capsases, enzymes that play an intimate role in programmed cell death. Their findings were unequivocal.

Apoptosis spread through the tube at a rate of just under 30 micrometers per minute – that is, about three-fifths of the width of a human hair. Most importantly, the waves showed no signs of diminishing in speed over a distance of several millimetres, This, the researchers conclude, provides clear evidence that trigger waves rather than diffusion are key to apoptotic cell death.

To rule out trigger waves as simply an artefact of using cell extracts in the mini tubules, the researchers did a further experiment with intact egg cells. It affirmed the presence of the waves. An additional finding was that apoptosis is, to some degree, dependent on the presence and concentration of mitochondria, the cell’s energy powerhouse.

“Thus, apoptosis spreads through trigger waves in both extracts and intact cells,” the authors write.

“Our findings show how apoptosis can spread over large distances within a cell and emphasise the general importance of trigger waves in cell signalling.”

The study appears in the journal Science.

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Paul Biegler is a philosopher, physician and Adjunct Research Fellow in Bioethics at Monash University. He received the 2012 Australasian Association of Philosophy Media Prize and his book The Ethical Treatment of Depression (MIT Press 2011) won the Australian Museum Eureka Prize for Research in Ethics.
  1. https://www.cancerquest.org/cancer-biology/apoptosis
  2. https://www.amazon.com/Human-Physiology-Biochemistry-Basic-Medicine/dp/0128036990
  3. https://www.scientificamerican.com/article/why-does-programmed-cell/
  4. http://tropicalfishaquarist.com/tropical-fish-compatibility-african-clawed-frogs/
  5. http://science.sciencemag.org/cgi/doi/10.1126/science.aah4065
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