Saturday, September 02, 2006

Journey into the cell 

Harvard University selected XVIVO, LLC, a Connecticut based scientific animation company, to customize and develop an animation that would propel Harvard's Molecular and Cellular Biology program to the next level of undergraduate education. XVIVO's recently completed animation, titled "The Inner Life of the Cell", has already won awards. The eight minute animation transports Harvard Biology students into a three-dimensional journey through the microscopic world of a cell. [See also this]

I can tell you a little bit about what's going on here. I should warn you, I'm not a biologist, just a fan.

We start off of course seeing white blood cells moving through a capillary blood vessel. Then a close up showing cilia from the white blood cell interacting with the cells lining the capillary wall.

We then cut to a confusing looking picture of a "platform" with some large molecules floating on a fluctuating surface. The surface is the cell membrane of the WBC, I'm not sure if this is the inside or the outside. Probably the inside. The molecules moving together are what they all a macro-molecular complex.

We then pull back and see a meshwork or net-looking arrangement. This is a structure just inside the WBC wall. These protein fibers give the WBC its semi-rigid shape, and by tugging on them it is able to change its shape and move around. Much of the interior of a cell is criss-crossed by these fibers, of various sizes. By building and disassembling them, the cell is able to control its shape.

We see some shots of these fibers and larger micro-tubules self-assembling. As noted above this is a little too "choreographed" and it is a more random process. We then see one being cleaved and beginning to disassemble, and some more disassembly.

One of the more striking sequences seems to show a big blob being towed along by a sort of foot that walks along. This is a vessicle being transported along a microtubule. It is destined to merge with the cell wall and dump its contents outside the cell. We don't see the fusion process, but near the end we see the completion of this, as a deep well in the membrane surface flattens out, and its contents are dispersed into the intracellular medium.

The "walking" process is again a little too regular. It is thought to be much floppier than this. The front end of the "foot" flops around until it hits the right spot, where it sticks. At that point an ATP molecule must bind (this is not shown) which drives the rear foot free of the tubule. It will then flop around itself until it sticks up front. This is a "brownian motor (or ratchet)" which is used in many places in cells.

We see a bunch of squiggly things shooting out of holes in some surface. I believe these are messenger RNA molecules coming out of the nucleus. The nucleus creates these molecules based on the genes which are inside the nucleus, and they go out into the cells where they serve as a guide to construct proteins.

That's what we see next, a greenish blob, the ribosome, slides along the mRNA and out the side of it comes a squiggly, new protein. What is not shown here is that there are millions of interactions with amino acids that are used to build the protein.

Many ribosomes are free floating as shown here but many are also attached to what is called the endoplasmic reticulum, a membrane within the cell that has a complicated shape. That's what we see next, a ribosome going down and attaching to the ER where it continues to work, producing a protein, then it detaches and separates into its two constituent pieces.

Next we see our friend the vessicle being towed along, and then a blobby, somewhat cylindrical object comes into view. Look close and you will see free-floating blobs moving through it. This big thing is a Golgi body, and its purpose is to prepare protein products for excretion from the cell. The vessicles move through it and some kind of last minute chemical processing is done (this is not shown, I'm not sure it is understood very well what happens there).

Back to a brief shot of the towed vessicle and then suddenly we see the end of its merging process, the volcanic upwelling as the vessicle completes its attachment to the cell membrane and finishes disgorging its contents.

Presumably this is some kind of signal the WBC is sending to neighboring cells, perhaps to prepare them for its entry.

We are back on the surface now, and see some molecules on the WBC link up to molecules on the adjacent cells. This is meant to represent the first steps by which the WBC "grabs hold" and is able to pull itself into the gap between the cells. That's how the movie ends, with the WBC disappearing into the body. SiliconEntity

Well, I am a bit of a biologist (I'm a med student with a masters in physiology), so I'll see if I can't provide a bit more detail...

The initial shot of a blood vessel is way bigger than a capillary (more like an arteriole), but those are certainly WBCs crawling along the inside. Those aren't cilia, but rather a variety of different cell adhesion molecules (CAMs), and cell recognition proteins.

The "platforms" floating around on the exterior surface of the cells are likely lipid rafts (which are quite fascinating, actually - a select, extremely hydrophobic lipid type accumulates around some proteins, and in some cases seems to dictate how and where they move around the exterior of the cell. In fact, they seem to be connected to the cytoskeleton on the inside of the cell - really cool stuff).

Most of what we see from here on out is not specific to WBCs, but rather processes that all cells go through. Those are actin microfilaments which form a mesh for structural support on the outer edge of the cell (near the membrane). Throughout the cell there are microfilaments, intermediate filaments, and microtubules, which give the cell structure, and more importantly, a framework for the movement of various organelles and vesicles around the inside of the cell (as we see in a little bit).

These are actin filaments being assemble initially (and then cleaved, and disassembled), and then after that microtubules are formed. They actually form in a very ordered linear manner like this. MT's form in long sheets that then fold over and seal to form a tube, then upon disassembly chip off, almost like shards of glass. MT's frequently fracture/shatter, while actin just breaks.

The part with the vesicle being towed along the MT is very cool - the parent post is quite right about the unrealistic steadiness of this molecule, but of course this is really the case for all the molecules. That tow molecule is probably either a kinesin or a dynein - these molecules are kind of like myosin (myosin and actin are what allow your muscles to contract), and one moves in one direction down a MT and the other moves in the opposite direction. We also see a distance shot of some centrioles (which are also composed of microtubules). Centrioles serve to anchor the microtubules that connect to the chromosomes and pull them apart during cell division. There are MT strands shooting out in all directions from the centrioles. One side anchors them to the cellular membrane and the other connects to centromere of the chromosomes.

Yep, those are definitely mRNA's shooting out of the nuclear pores. They form a ring as the two ends form a complex that initiates translation of the mRNA into protein. The ribosomes then latch on and start cranking out protein. As the protein emerges from the ribosome we can see it start it folding process. Protein folding is a very complicated and intricate process. If a protein is misfolded it may simply not work, or it may cause a disease state. Creutzfeldt-Jakob disease (caused by mad cow disease in some instances) is caused by misfolded proteins that then cause other proteins to misfold (it's a prion encephalopathy).

We then see some sort of protein-protein interaction occurring randomly out in the cytosol of the cell. This could be any number of
things, but looks to me like a signaling protein interaction. That newly formed protein dimer could then float off and effect some other cellular process (presumably something those two proteins couldn't do by themselves). Also, that big gray thing in the background that they float by - if I had to wager a guess, I'd say that was a mitochondria.

We then see a protein fold through a membrane in the rough ER.

We then see what looks like vesicles budding off of the ER and floating off, presumably to the Golgi apparatus, which is what we see next, right after more of the vesicle being towed again. The Golgi preps things for extracellular and intracellular transport. The golgi often sends the proteins it modifies (the golgi frequently serves as the site where sugar molecules are attached to proteins and other post-translational modifications occur) back to the ER for further processing, or it could send them off to another organelle or out of the cell. It all depends on what surface proteins are in the membranes of the vesicles. These proteins direct the vesicles to where they need to be... and they are often towed along the train tracks made of cytoskeleton, as we keep seeing.

We then see a vesicle dumped into the extracellular space, and all of its contents go flying out. Some appear to be membrane proteins that are attached to the cell itself.

We then see a lipid raft form on the surface of the cell. You can see a bunch of a certain type of lipid in the membrane go flying through the membrane to get close to the proteins that begin to group together. This is super freaking cool.

We then see some activated CAMs and signaling molecules. These are required for a WBC to move out of the blood stream and into and between tissues. WBCs hang onto the wall of the vessel and will actually signal for the cells lining the vessel to loosen the connections between them so that the WBC can crawl out.

The WBC is then seen sliding along the inside of a blood vessel. Its shape goes through a radical reformation wherein it breaks down much of its cytoskeleton and reforms it into a new, flatter shape so that it can slide between the endothelial cells of the blood vessels easier.

This animation is super freaking cool, by the way.

Now I need to tear myself away from /. and go study this kind of shit some more. - jrau

posted by George Thomas Kysor 6:50 PM