Like a lot of people, I enjoy tickling living things to get a response out of them. It doesn’t hurt them but you sure know they’re very much alive! Grandkids are one example. In some cases, however, “tickling” is irreversible. Tickle a tarantula with a stick and you’re liable to get covered in urticating hairs they spray out from their body. If you tickle a cell nucleus in just the right way, however, the whole thing starts to deconstruct right in front of your eyes. I know because I did it many years ago at Ohio State University. Not only did I facilitate deconstruction of nuclei, I seem to have done so in various stages of the cell cycle so that all of the pieces parts changed from one phase of the cell cycle to the next. Boring, right? Well, give me a chance here, ok? I know this is a tough crowd here.
If you ever took a biology course you should know something about the cell cycle. Most of the replicating cell exists in what is called S phase where the DNA is being synthesized so the cell can split into daughter cells. When all of this is done, there exists a brief moment in the cell cycle where the duplicated chromosomes condense and are easily seen under a light microscope. They line up in the center of the cell where they split apart so each new daughter cell gets an equal share of the DNA via daughter chromosomes.
Ok, enough of that already, I don’t want your brain to explode. Let me show you some pictures, instead. Please excuse me if you’ve already seen them but I need some visuals to make a few points here. I’ll make it as simple and brief as possible:
This is a picture of mouse L-1210 cancer cells just placed under the microscope. They have been stained with a dye called acridine orange that makes them light up in the dark under ultraviolet light. The larger cell has probably just duplicated its DNA and is getting ready to divide. You can just see a vague outline of the nucleus here. These cells have a very small amount of cytoplasm outside the nucleus. The orange inclusions inside the cytoplasm (second arrow) are probably lysosomes that are used to digest material within the cell. This dye stains double stranded DNA as yellow or green and single stranded DNA or RNA as orange or red. However, under acidic conditions as found in lysosomes, it will glow orange or red.
Images 1-3 are probably naked nuclei since no orange “lysosomes” can be seen. These nuclei begin to swell until they are huge. This is because they are dying from lack of nutrients and/or oxygen deprivation etc and constant irradiation with ultraviolet light under the microscope. Note the presence of “blebs” in images 2 and 3 popping out around the edges of each nuclear body. These blebs have dark green rings around their edges. The nuclear body in image 3 has degraded enough that large vesicles have formed. A smaller vesicle has migrated out of the nuclear body attached to a filament with a smaller leading filament attached at its front.
So what the heck is going on here? Well, let’s look at some more pictures:
Flabbergasted yet? At first glance, this looks like the cell culture was contaminated by yeast or protozoa. These structures are far too big to be bacteria but are very similar in shape, just like a chain of yeast. However, these structures were not there initially, so they must have originated from the mouse cells.
The structures in this photo are different in size, shape, coloration and orientation. They also appear to be migrating along green hollow tubes with an exit strategy in mind. Other bizarre structures can also be found:
At first glance, this seems like absolute chaos in action, but when you consider the cell cycle it starts to make more sense. Many of these objects have a circular motif with or without central hubs. There is also a hierarchy as to how they are put together. Some of these circles contain even smaller circles with or without hubs. In others, there are no circles but discrete rod shaped particles. Some are arranged in concentric circles whereas others seem to be attempting exit strategies to the periphery of the main structure. Finally there are still others where the rods seem to connect together in a structure very similar to chromosomes. They seem to be derived from more circular elements that are breaking up into large, linked rods.
In summary, it is unfortunate that each of these structures were not videoed in real time because many of them seem to be transitioning into the others. They also need to be studied using techniques like immunostaining to get a better idea of their chemical compositions. Of course, this could still be done, but it would require funding and laboratory space to do so. In any case, it is quite obvious there is still much to be learned about how our DNA is really put together inside of our nuclei. Otherwise, we continue just shooting in the dark when it comes to medical advances.
You can learn more about my research by clicking on the tabs above this post.