There’s this article in the popular press titled “Scientists calculate the speed of death in cells, and it’s surprisingly slow”, and the title is backwards. It’s summarizing an article in Science magazine which measured the speed of a wave of apoptotic signaling in dying cells that concludes the exact opposite: cells die fast.
Apoptosis is an evolutionarily conserved form of programmed cell death critical for development and tissue homeostasis in animals. The apoptotic control network includes several positive feedback loops that may allow apoptosis to spread through the cytoplasm in self-regenerating trigger waves. We tested this possibility in cell-free Xenopus laevis egg extracts and observed apoptotic trigger waves with speeds of ~30 micrometers per minute. Fractionation and inhibitor studies implicated multiple feedback loops in generating the waves. Apoptotic oocytes and eggs exhibited surface waves with speeds of ~30 micrometers per minute, which were tightly correlated with caspase activation. Thus, apoptosis spreads through trigger waves in both extracts and intact cells. Our findings show how apoptosis can spread over large distances within a cell and emphasize the general importance of trigger waves in cell signaling.
To put that in context, 30 µm/min is more than 40,000 µm/day, or 40mm/day. Back in the day when I’d stick proteins in one end of a cell and wait for them to get to the other end, we’d estimate that the rate of transport was a couple of millimeters per day — so if you were working with an axon that was a couple of centimeters long, you might have to wait a week or two for a complete traverse. I’m impressed with 30 µm/min.
Another way to look at it is that if your typical cell is about 10µm across, once the apoptotic enzymes in one spot are activated, the whole cell is self-destructing in 20 seconds. The pop sci article uses a different example: “That means, for instance, that a nerve cell, whose body can reach a size of 100 micrometers, could take as long as 3 minutes and 20 seconds to die.” That’s still fast. That’s faster than diffusion. The authors ruled out diffusion as the mechanism, and suggest that it’s a wave of activation.
The unusual size of the Xenopus egg raises the question of how an all-or-none, global process such as apoptosis spreads through the cell. One possibility is that apoptosis spreads through the egg by random walk diffusion, ultimately taking over all of the cytoplasm. A second possibility is suggested by the existence of multiple positive and double-negative feedback loops in the regulatory network that controls apoptosis. These loops may allow apoptosis to propagate through self-regenerating trigger waves. Trigger waves are propagating fronts of chemical activity that maintain a constant speed and amplitude over large distances. They can arise when bistable biochemical reactions are subject to diffusion or, more generally, when bistability or something akin to bistability (e.g., excitability or relaxation oscillation) is combined with a spatial coupling mechanism (e.g., diffusion or cell-cell communication). Familiar examples include action potentials; calcium waves; and the spread of a fire through a field, a favorable allele through a population, or a meme through the internet. Trigger waves are an important general mechanism for long-range biological communication, and apoptotic trigger waves may allow death signals to spread rapidly and without diminishing in amplitude, even through a cell as large as a frog egg.
That makes sense. The apoptotic enzymes are distributed throughout the cell in an inactive state at all times; you don’t have to physically move the proteins around, you just have to switch one on, which then switches on its neighbor, which switches on its neighbor, and so on.
I’ve seen many cells die, as I’m watching them in the microscope. It’s always impressively swift and thorough: one minute, round, plump healthy cell; next minute, membranes are blebbing out all over the place, the cytoplasm goes all granular and curdled, and at the speed of light I’m cussing over yet another failed experiment.
I’m not sure why the editor or whoever slapped that confusing title on the article. There may have been some confusion about scale: a 2 meter tall human doesn’t die by the propagation of a signal from a single point on a cell, spreading at a rate of 40mm/day (if it worked that way, you’d stub your toe, a cell would die, and you’d have to wait a month and a half for the death signal to reach your brain). That would be slow. Multicellular organisms die by systemic failure of a network, not the progressive collapse, cell by cell, of all of its components.