Editorial notes: This scientific analysis was found as a ‘draft’ entry in Everything2. It was last updated on 03/05/2011.
In 2006 Harvard presented a short movie they’d contracted called The Inner Life of a Cell. This eight and a half minute production was a 3D animation of (ostensibly) what a cell could look like on an atomic level*.
This forms the final chapter of my three-part introduction to molecular biology. If you haven’t read the other three parts yet, perhaps you’d like to do so now. If you haven’t and you’re not inclined yet, go ahead and watch the movie, maybe that John Williamsesque score will inspire you.
The following is an explanation of what goes on in the video. It’s not thorough. Its purpose is to help contextualise some of the things I’ve written in the previous parts. If you already have a molecular biology background you might want to skip down past the next bit to the bottom where I’ll have a short critique of the film.
The previous chapters of this introduction had introduced atoms and their relation to proteins and described the relationship of DNA to RNA to proteins.
How to coordinate this? Some of you might want to watch the film in its entirety first. Try and get a high-quality version and watch it in full screen. Note that there are different versions out there, some with the original music, some 3minutes (preview), some the full 8.5minutes, and some with the original commentary (which is technical). Presumably, your local video website has them all. Afterwards, I’d recommend opening this page up and also the video in a small window on top of this page. It might be helpful to know that there are websites that download youtube films onto your computer, although you’ll need an appropriate program to read them. Most people enjoy the one with the music. Please don’t ask me for a link 😉
Plot summary: An immune cell is needed to attack some disease. It travels through the bloodstream until it gets a signal to stop. It now needs to crawl in between the blood vessel walls to get to the infected area. To do this the cell makes new proteins and sends them out to the outside of the cell where they can grab onto the blood vessel walls.
The times listed below are approximate and vary with videos. My reference video was 8:12 minutes long (I used the one with the voiceover).
0:00-0:54 – A white blood cell crawls along the blood vessel wall with grabbing proteins
The film starts off with blood rushing through a blood vessel (e.g. a vein or artery) and a white blood cell trudging along the vessel wall. The main force moving the white blood cell or leukocyte – which is an immune cell responsible for attacking threats – is obviously the blood flow around it. But leukocytes are generally not in a rush, and when not on the job are just patrolling.
We soon see grabbing proteins sticking out of the leukocyte (purple) which reach onto proteins sticking out of the blood vessel wall (yellow). This is one way the cell is holding onto the wall as it rolls along.
The cell has heaps of little bumps where it concentrates these grabbing proteins, and the grabbing proteins are designed to let go and grab on as needed. Continuously. All the time. Countless of them.
0:54-1:54 – The cell receives a signal that there’s inflammation nearby
A bit of background is needed for this scene beyond what I’ve given previously, but only briefly: the actual wall of human cells is called a membrane. The membrane is made up of phospholipids which are molecules that are sperm shaped with the head sticking outwards and the tail on the inside. The membrane is double layered. They show a cross-section in the film which makes this obvious.
One way the cell carries proteins around the membrane is on rafts. These are part of the membrane, but their molecules are less flexible, and so can stick together and essentially float through the membrane sea of molecules, while carrying their loads. There’s aren’t important for the story… yet.
Now, something important happens. This spot in the blood vessel is near a site of inflammation, and so needs the leukocyte to exit and do its job. It tells the leukocyte this message by presenting special inflammation molecules to it. In the video, we see this as the little yellow molecule presented by the orange protein to the receptor protein on the leukocyte surface. This sets off a whole host of other events on the inside of the cell – which is where we’ll be going shortly – but keep in mind that this is happening all over the leukocyte’s surface, not just in this one spot. In any event, it will result in the leukocyte making a “decision” to go to the site of inflammation.
1:54-2:13 – News of the inflammation is conveyed to the inside of the cell
As soon as we get inside the cell you can see the cell membrane from the inside – including a raft floating off, and also parts of the cell’s skeleton – called cytoskeleton – which are the various long structural protein-links you see. Important now is to keep in mind that when the inflammatory signal was received on the outside, it causes the receiving protein to change on the inside. The receiving protein is transmembrane, meaning that it spans the membrane width.
Note that we don’t actually get to see how that signal is conveyed, but most likely the inside of the receiving molecule modified some proteins it was associated with, and those went off to do other things, and so forth.
2:13-4:12 –Seeing the highways which will serve the cell’s response
Now we get to focus on some of the cytoskeleton types. I won’t go into them, but you see both those that sit on the surface and those that go deep into the cell.
Cytoskeletons are built in a modular manner and are extended with lego-like protein units, and we get to see some of these built and taken apart.
An important type of cytoskeleton – for this video – are microtubules which are seen as the green tube structures. They’re far sturdier than the previous cytoskeletons we saw, and are used as highways for carrying things inside the cell.
The cell has received word of the inflammation and will need to make and carry new proteins to the membrane as part of its response. One way it can carry proteins is by making small balls of the membrane and putting the proteins of interest inside them. These cargo balls can be attached to a powerful protein motor unit, which slowly drags it along the microtubule.
4:12-4:35 – Seeing some of the major players the cell will use to response
We also get to see some other areas of the cell which are affected by the cytoskeleton, including:
Mitochondria – the energy factory of the cell (seen as the slug-like structure) – the leukocyte might need to step up energy production in preparation for dealing with inflammation.
Endoplasmic reticulum and Golgi – factories for modifying protein (seen as a collection of blobs in the distant right around the same time we see the centrosome) – these will be involved in modifying the many new proteins that will be made to deal with the inflammation.
Centrosome – the place from which microtubules start out (seen as the sphere from which the microtubule emanate) – the cell may need to send out new microtubule as highways for transporting some of the new protein cargos.
4:35-5:38 –New proteins made to deal with an inflammatory response
The cell has received the signal and new instructions for protein manufacture have been copied from the DNA in the form of mRNA (messenger RNA). The mRNA is seen being sent out of the DNA’s housing where it forms a loop and is read by a (green) group of proteins (ribosome) into a protein.
There will be instructions for all sorts of protein, varying from structural proteins, to signalling proteins, surface receivers, to attacking proteins for dealing with any possible threats.
The leukocyte needs some of the proteins for activities inside the cell, but others it will need on the surface or even outside. For these, the ribosome gets hold of the mRNA and then attaches to the endoplasmic reticulum (which we saw above) and makes the protein straight into it.
5:38-6:32 – Select proteins are designed to be sent to the surface
As just stated, some of the proteins will be needed to be placed into cargo balls and taken to the surface. The endoplasmic reticulum sorts these and packs them accordingly. We see them bud off here and then carried off.
Before arriving at the surface, some of these cargo proteins will need to be adjusted, and so the cargo is taken to the Golgi (which is similar to the endoplasmic reticulum) where it undergoes various layers of sorting and modification. By “modification” I mean that small molecules are removed or added.
Once that’s done, the cargo can continue to the surface.
6:32-6:42 – The new proteins reach the surface membrane
When the cargo reaches the cell membrane, it literally fuses with it. The proteins which were inside the cargo are released outside the cell, while those that were part of the cargo’s membrane are now part of the cell’s membrane.
6:42-8:00 – the new protein is responsible for grabbing tight and stopping the cell’s motion
Do you remember at the beginning when the cell received the inflammation molecule news? That caused the receptor molecule to change its shape and cause other proteins and molecules inside the cell to signal. That resulted in all sorts of things, including the production of new proteins.
It also resulted in processes which made new rafts on the membrane and caused specific proteins to cluster inside them.
The new proteins that the cell just made are clustered into rafts where they’re ready to do their job. They look similar to the grabbing proteins we saw at the movie’s beginning, but they’re slightly different. These proteins are much stronger and don’t let go. They stop the leukocyte where it is so that it can squeeze itself in between the blood vessel walls.
The entire pathway we saw was just one small part of what made the leukocyte stop. And countless other activities are involved in each of the countless steps which make it possible for a leukocyte to get out of the bloodstream, and eventually reach the site of inflammation and deal with what it finds there.
Fin.
I could comment further on what we just saw, but I’d hope I don’t need to. I also hope that this write-up achieved some of its intentions. I would appreciate any feedback on what it may not have achieved, and would also be interested to hear whether there was some process you saw which was too incredible which I might be inclined to write-up on… Thanks.
* A very short critique, really just meant to highlight ONE MAJOR SIGNIFICANT limitation of the film which can be misleading. Everything in the movie floats in the right direction to be helpful. Chaos doesn’t seem to an issue. Essentially, this is what a cell would look like if it was designed by a watchmaker. If I may be gnomic at last, then I would remind you that biology is order through chaos.
