Microtubules – Bucatinis of cells


Cells are weirder than the simple illustrations in your biology text book. Look at this dendritic cell illustration:

Patente Thiago A., Pinho Mariana P., Oliveira Aline A., Evangelista Gabriela C. M., Bergami-Santos Patrícia C., Barbuto José A. M. Human Dendritic Cells: Their Heterogeneity and Clinical Application Potential in Cancer Immunotherapy Frontiers in Immunology Vol 9, 2019 DOI=10.3389/fimmu.2018.03176, CC BY-SA 4.0 https://creativecommons.org/licenses/by-sa/4.0, via Wikimedia Commons

and compare it with electron microscopy (real) image:

Natural Killer Cells Basic Science and Clinical Application 2010, Pages 239-253

Besides the immature/mature distinction, cell can have a variety of shapes. Shape is important and often it is coupled with function. Cells can actively maintain their shape by utilizing their “skeleton” (cytoskeleton).

What is this cyto(=cell)skeleton?

Cells produce lot’s of proteins for different functions. Some catalyze biochemical processes, some regulate other proteins’ functions, some sense the environment and some of them are there for structural reasons.

3 main (there are also others) groups are actin filaments, intermediate filaments and microtubules. Each one of these are fascinating and there is a lot to know about them but I will focus on microtubules. It is assembled by α- and β-tubulins (2 proteins=) dimers. In the animation below, you can find these in red/blue (β-tubulin) and green (α-tubulin). Both of these molecules bind to GTP. A chemical similar to famous ATP (energy currency of cells).

Only one β-tubulin bound GTP hydrolyzes after assembly over time (blue->red). Hydrolyzation in this case means GTP loses one of the phosphate groups. tri(=3)phosphate becomes di(=2)phosphate. Hence, GTP becomes GDP. This growth doesn’t continue forever and eventually leads to a catastrophe.

Eva Nogales lab, University of California, Berkeley

Well, above is a computer animation but does this happen in reality?

Below is a live microscopy video showing microtubules growing and shrinking.

They also function as highways in the cells for transport.

And of course this was also imaged:

Above you can see green labeled motor proteins (kinesins) moving along red labeled microtubules.

Ok, I hope I got you interested in microtubules. And if you are a biologist, you will probably say “so what?”. But the main reason, why I am writing about them is not what they are but what is inside, or what isn’t?

There has been a lot of research about their structure, chemical modifications and even physical properties such as stiffness. We know many proteins that bind to microtubules with specific functions. We also know a lot about how they grow or shrink. Now, many of these things are either happening outside or observed from outside. However, we know very little about the inside of microtubules aka lumen of microtubules. Our understanding about the lumen is surprisingly limited. In biology, space is limited. All those illustrations of cells with big empty spaces between membranes aren’t realistic. In reality, cells are packed densely. Often bunch of proteins and other molecules glide over each other. Here is a nice illustration of a more realistic inside of a cell.

Then it is fair to assume that also microtubule lumen should have “something” with a “certain function”. Right? Well I thought so at least. But I was puzzled by the lack of results I could find. One interesting bit of information is related to acetylation of microtubules. This means a chemical modification is performed by an enzymes. This modification is done on an aminoacid called lysine 40 (40th aminoacid) in α-tubulin. Interestingly, this aminoacid is inside (within the lumen side) of the protein. Somehow, the enzyme needs to access there to make the modification. But how? Lumen is quite isolated from outside. There are limited openings at the ends so diffusion must be limited. Once idea is that the microtubules bend and split shortly to allow diffusion. Some monomers might detach and reattach creating temporary windows/cracks. Nevertheless, there is only 15nm space in the lumen plenty for proteins but only if they can get there somehow. Another idea is that once the enzymes enter there, they can rapidly diffuse. However, it looks like a strong binding between the enzyme and the microtubule would take too long to reach an equilibrium. It is also possible that the enzyme weakly binds, therefore allowing faster diffusion. You can read more about this part here:

Causes and Consequences of Microtubule Acetylation

Similar to that idea, it was speculated that the lumen might act like diffusion highways between 2 points. Besides that, there was an interesting discovery not so long ago.

In situ cryo-electron tomography reveals filamentous actin within the microtubule lumen

In this study, researchers discovered actin like structures within microtubules.

Actin is another cytoskeleton structure, which also is a multimolecule complex. But only one type of protein is involved (in general). It doesn’t have any lumen, it is smaller and can fit inside. Of course the big question remains:

Well, more research is needed to answer if this occurs regularly and if it has any function.

Now that we have this behind, let’s dive into weird world of quantum physics. I am in no position to explain quantum physics but I still find it fascinating. Some scientists postulate that microtubule itself and the lumen may have quantum behavior in the wet and warm cells! They go even further to suggest that this could be key to consciousness or so called quantum consciousness. Microtubules play a very important role in neurons and neuronal cell shape. They connect long distances within dendrites and axons and support these structures. Could they also act as information transfer systems? Could quantum behavior of microtubules act as core of true consciousness? Well, this is hypothetical and many scientists doubt it. First of all, cellular environment is not very suitable for such processes. That’s why we need to make our quantum computers super cold. But the idea is fascinating. Oh and very famous scientists are behind the idea and are working on it. Now I will finish with the following video, which is a must-watch in my opinion.

Teaser terms: there are “bings”, neurobiology, philosophy, quantum channels

Life inside a microtubule

What is inside a microtubule?