I was introduced to hagfish at Gulf Specimen Marine Lab after viewing the video of Joel Sartore preparing to photograph a hagfish specimen for Photoark that was graciously provided by Dean Grubb via their research vessel The Apalachee. You can see the video here.
So what’s with this slime? Hagfish are a class or marine organism that stands alone. They have skulls. They don’t have a spine. There are several species ranging in size from a few centimetres to well over a meter. They have simple light spot eyes that allow them to sense light and dark but not form any real image. If something grabs them they can literally fold themselves over in a knot while releasing copious quantities of slime as a defence. The slime deters predators and may even kill an attacker by clogging the gills until the predator suffocates.
The slime itself is fascinating stuff. It has the strength of spider silk and yet can be stretched into sheets (as the video shows). We had some people visiting who wanted information on the topic and so I decided, at Jack’s request to do some background reading. What I found was fascinating.
The cell state splitter is made of three cytoskeletal components, microfilaments, microtubules and intermediate filaments. The organelle is located in the apical end of the cell that is in a sheet epithelial cells one cell layer thick and joined by protein structures and passages like cellular rivets allowing communication with the cell. In our model of the cell state splitter we have a bistable organelle made from a microtubule mat pushing outward, a microfilament ring closing inward. The two are in a tug of war and they are in balance when a cell is competent to differentiate. There is an intermediate filament ring below that which provides stability and prevents the organelle from being influenced by random minor fluctuations. A strong mechanical perturbation starts a wave of contraction or expansion through the cell sheet propagating one of two possible signals. Those signals are sent via signal transduction pathways to the nucleus and the pattern of gene expression changes.
While we did extensively review the role of microtubules and microfilaments we really didn’t look very hard at that intermediate filament ring. My encounter with the hagfish has me rethinking that. If you watch the individual cells as they participate in the contraction wave you see the cell contract and then return to its original shape. However the expansion wave is very different to observe. The expansion looks like a series of small jerks and then suddenly the apical end “gives” and expands rapidly. In the axolotl cells at least, the apical end spreads to double or triple the diameter and then stays that way. We knew that intermediate filament ring needs to “get out of the way” in some fashion but we never considered what the mechanism might be.
Back to hagfish slime. Hagfish have little pouches under their skin that form small hollow balls lined with a single layer of cells, an epithelial sheet. Cells within that sheet that are presumed to be stem-cell like, divide and produce two types of daughter cells. (In our book we referred to such activity as Type 5 Cell Sheet Differentiation.) One type of daughter cell begins producing a mucus and the other type fills with a specific highly modified and specialized intermediate filament. Once the cells with either slime or mucus are totally packed full, the cell undergoes a programmed cell death and this leaves sacks made of plasma membrane packed full of either mucus or the tightly coiled intermediate filaments. The intermediate filaments look like a tiny solid wasp nest only 5o um in with. This repeated cellular differentiation off the epithelial layer fills the empty space of the little pouches the hagfish have under their skin.
Along comes a predator who does something to upset the hagfish. The hagfish responds by contracting those pouches and squirting the dead cells full of slime or intermediate filaments. The opening through which the material is forced is small enough that the plasma membrane is ruptures and stripped off and a bullet of tightly coiled intermediate filament or mucus is produced. The intermediate filament and mucus take up water. The result is slime.
Intermediate filament have a neat property known as alpha/beta transition. The proteins involved can have a short tight coil or they can have a zigzag straight string and they can flip between these two configurations. Some external force has to be applied but with the right additional force the flip can happen. If you have ever applied heat to a wool sweater and had it shrink to much smaller and denser version, you have induced the alpha/beta transition by applying heat. Hagfish intermediate filaments fill the second cell type in the highly compacted state. When they take up water they under a transition and dramatically lengthen. The tightly coiled wasp nest “skeins” spread and grow, mixing with the mucus to produce the slime. The process of changing this tight 50um ball into many threads of 150mm long fibres takes only seconds. Ions from salt water play a critical role though exactly how this works is not known. However these are the same ions so important in signal transduction during differentiation. (You can see a neat picture at the link but Nature didn’t I’ve me permission to use it.)
And so our adventure with the slime salty tasting hagfish slime inadvertently provided us with a valuable hypothesis on exactly how the intermediate filament of the cell state splitter “gets out of the way” of an expansion wave. That ring likely undergoes some kind of alpha/beta transition stimulated by the same ion flux that is involved in signal transduction to the nucleus.
I suppose I should not be surprised that the new clues to functioning of the organelle of differentiation can be found in a simple creature from the bottom of the sea. After, all life on earth arose from some common ancestor and the cytoskeleton goes all the way back to that common ancestor. Still, I find it amazing. When I was a child my favourite bit of verse was by Robert Louis Stevenson:
The world is so full of a number of things
I’m sure we should all be as happy as kings.
Those things include an ugly little hagfish from the bottom of the sea.