Slimy hagfish cells adapted to deter predation

HAgfish are known for their defensive slime, which can go from a small secretion to a load of goo in a fraction of a second. Slime is a meandering web of fibrous protein threads that trap the surrounding seawater, turning it into malicious slime that chokes the gills and jaws of attacking predators.

courtesy of yu zeng

The biology of this slime has long fascinated materials scientists and evolutionary biologists, including Yu Zeng, an evolutionary biologist at Chapman University in California. Zeng and his colleagues decided to focus on the glandular cells that produce the smooth substance of fish, and in their September 20 article in Current biology, they find that these slimy cells differ in size and produce different sized threads depending on the size of the hagfish, with the larger hagfish having much larger thread-producing cells than one would expect based on only on the size of the body. These larger cells produce longer and thicker threads, resulting in a more viscous mud capable of deterring even the largest underwater predators. Zeng postulates that the size of the cells may have changed to repel the various predators of hagfish, large and small.

The scientist spoke with Zeng about the new paper and hagfish in general to learn more about the slimy superpowers of these strange deep-sea fish.

The scientist: What interested you in the study of hagfish cells in particular?

Yu zeng: Hagfish are just weird. They are so remote from our mundane human life because they live in the depths of the ocean. They don’t have a face, don’t have eyes, and look alien. We know very little about their life history, so anything about hagfish is, by default, interesting.

In this particular project, we are studying the morphology of the cell that generates this thread. The thread is an essential component for their defensive slime, [and] is also a really, really weird structure.

The bigger picture is. . . . The larger hagfish would be eaten or attacked by larger fish. And then the smaller species would be attacked by smaller species of predators, and then they live in different depths of the ocean. . . . We wonder if the cell[s] which produce the threads, and then the threads themselves, change with the body size of the hagfish. In other words, do larger hagfish have stronger armor against predators?

pacific hagfish (Eptatretus stoutii) in a net

Courtesy of yu zeng

ST: About your research process: did you encounter any challenges?

YZ: I can start with the simple challenge which is access to the specimen[s]. . . You can buy freshly caught specimens from fishermen,. . . but there is only a limited number of species [available this way]. . . . If we want to compare between a lot of species then we have to sample museum specimens. These are preserved specimens captured by accident during surveys throughout history. Some are decades old. Some are fragile. So, in this study, my co-authors investigated the one[s] in the museum, [and] sampled glands from pickled specimens.

The second challenge is a little more mental, because every time I see them it reminds me of those alien movies. They don’t have a lower jaw, so when they open their mouth, the mouth flexes and unfolds from the inside out with two side jaws. It does not open from top to bottom but unfolds. So it’s really weird.

And I would say that a third challenge is to connect all the dots at different levels. In this particular study, we are connecting dots on the size of the body, and on the size of the cell that makes the thread, then on the thread. So I have to develop models to link these different levels. The whole animal is a level of things, it is the whole animal that interacts with predators. And then there is [the] cell – physiology and mechanics. . . . And then the third level, the wires.

I [had] to develop a model to help us estimate the size of the wire, because when we sample the wire, it’s a skein packed inside the cell. You cannot directly measure the wire because it is super thin. And it’s hard to pull off. . . a wire then use micro tweezers [to] unfold it, untangle it, then stretch it and measure it. It is almost impossible. You can break the thread at any time. . . Then when I have all this data, I have to write scripts, like computer programs, to do analysis.

ST: Is there something that surprised you?

YZ: [The] extreme allometry, [which is] basically how cell size changes[s] with body size. . . [for the thread-producing cells] this coefficient is greater than all previously documented cells. So this means that the cells get very big to produce the threads.

This is surprising because the cell size is relatively constant in animals. We show how much cell scaling exceeds scaling in other cases, as in [mammalian cells]. [This will] help us understand the flexibility of animal cells and provide new knowledge about the mechanism that drives cell size changes.

ST: The article mentioned that the mucus threads of hagfish are the largest known intracellular polymer. What does it mean?

YZ: This means that the cell must be really specialized and. . . as the cell grows and becomes extremely large, it needs a more powerful power system. It takes a lot of energy to grow protein. . . . [The cell also] needs another mechanism[s] be structurally rigorous. . . [so it] will not be easily deformed.

We suspect that the growth of these glands, the filiform cells, is fueled by other cells around [them that] pump energy to [them] and materials for making new threads. Then the majority of the cell is occupied by the wire. . . . Cell nuclei [are] really, really small,. . . less than five percent of the volume. So this means that the cell has abandoned many other organelles to be able to make the wire.

Scanning electron microscopy images of skeins of hagfish yarn

Courtesy of Gaurav Jain

ST: Where do you see the future of this research? What would you like to explore?

YZ: This article is part of a project where we are studying how hagfish make threads. I’m trying to figure out how this whole set or skein of threads develops – how it goes from little to big, and how it forms, because to make a skein, [the thread has] have a lot of curls, and [the cell has] to wrap curls effectively. How is conditioning done within a single cell? This is one of the orientations in progress.

On another level, I would be interested in understanding the evolution of the thread. What is the origin of this cell? What is the previous form? Because everything you watch [at] which is so complex and specialized has a simple and ancestral form. It’s derived from something that’s not so alien, not so specialized, something more normal. This process of transitioning from a normal, simpler and less specialized form to this specialized form is interesting. And this is the coup de Mars. The first one I mentioned is probably the moon shot, then this one is the Mars shot. Understanding the origin of these complex structures involves many fields – cell biology, biomaterials, biomechanics, geometry, computer science, materials science – and a lot of programming to be able to bridge all these fields.

Editor’s Note: This interview has been edited for brevity.

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