Nerd Porn

The Inner Life Of The Cell is definitely the coolest biology video I've ever seen. (Not that there's that long a list, but it's definitely awe-inspiring.) It tells the story of the processes involved in how one macrophage (a blood cell) senses a signal and decides to leave the blood vessel and enter the surrounding tissue to respond to an injury or infection. The macrophages are part of the innate immune system and are one of our first lines of defense against injury. In the blood, they move rather slowly, like cops on patrol, rolling along the blood vessel walls. When they sense the distress signals that injured cells put out to call them to the scene, they stop rolling and slide between the endothelial cells that make up the blood vessel wall, then keep moving until they reach the site of injury and can start cleaning up the mess. The video starts at the cellular level (in the blood vessel) and then shows all of the molecular processes involved in making the macrophage stop, then brings it back out and shows the macrophage slipping between the endothelial cells to enter the tissue. All of the proteins depicted look like they have been based on the 3D structures obtained from x-ray crystallography (in which you can actually shoot x-rays at a crystallized protein and actually "see" the structure rather than guessing at it), and then those images have been animated to show the dynamics within the cell. So basically, the pictures (even of molecules) are actually based on data and not just animated randomly. Anyway, you have to see it to really understand, but it's absolutely amazing!

I realized when I was about to post this that I wasn't sure how many people would realize what they were seeing. So I decided to do a little walk-through to explain what each scene is depicting. There is no timestamp on the movie, so I just numbered each scene change. I tried to keep things in lay terms but also give the scientific vocab for those that were interested and explain what's going on. It's long, but I think the movie is so much more beautiful when you realize what everything is. (*Note: I didn't make the video and this is just my interpretation, so I can't vouch for its complete accuracy.*) Anyway, here goes...

1. Blood cells flowing through a vessel. The fast red ones are red blood cells, the slow, blue ones are macrophages rolling along the vessel wall, patrolling the area and looking for signs of trouble.

2. Close up of the macrophage's interaction with the endothelial cells that make up the vessel wall. The bumpy thing on the bottom is the macrophage and the top smooth part is the blood vessel wall.

3. Extreme close-up of the proteins on the surface of the macrophage and vessel wall. The yellow proteins sticking out from the vessel interact with the purple receptor on the macrophage.

4. Same as 3, but zoomed out. The yellow proteins on the vessel wall are the signal being sent from the vessel to tell the macrophage to stop and pass through. The interaction is more stable than the normal, transient interactions that let the cell roll along, but still not enough to completely stop the cell.

5 and 6. The outer surface of the macrophage underneath the outer surface of the blood vessel. The membrane is called a "fluid mosaic" because while the structure can stay the same, the pieces are all free to move around. The circular thing that seems to be floating on the moving balls below it (that is zoomed in on in 6) is called a "lipid raft." Scientists think that although most of the membrane is free to move fluidly, there are globs of lipids that stick together and hold particular membrane proteins together to create little units that can interact and do what they need to do quickly, without having to bump into each other among the waves. The yellow things sticking up from the raft are receptor proteins, and the flat part is the lipid bit of the raft. Note you can still see the interaction of the yellow and purple proteins in the background of these shots (as well as in 7).

7. Still looking at the interaction between the macrophage and blood vessel. The red glob in the middle is extending from the blood vessel. Again, you can still see the yellow and purple fingers that are holding the cells together.

8. Close up of the red protein. It is extending its yellow piece to signal to the brown receptor protein on the macrophage cell surface. This is probably the signal to tell the macrophage to not just stop, but actually go between the vessel wall cells and go into the tissue, but a lot needs to happen for the macrophage to actually respond to that signal.

9. We're now looking up at the macrophage membrane sheet from the inside, as if we were just on the surface of a swimming pool and we're now down at the bottom and looking up at the surface. The flat blue thing with the small red protein that's moving to the right is the underside of the lipid raft we saw before. The big globs that look like the bottom half of people in the pool are the bottom half of cell-surface proteins that act as receptors.

10. Not sure. Seems like we're looking down on the surface of the cell, but I don't know what the big interlocking lines are.

11. We're moving down through the cell and looking at the structural elements ("cytoskeleton"). The cell isn't the bag of water and random, floating proteins a lot of people think it is--it's actually filled with tons of structural elements, like beams and rods in a building, that hold it all in the right shape.

12-13. Showing the assembly of one of these big beams ("actin"). It's made of lots and lots of the same piece, kind of like building a tower out of legos. The cool part, though is that they all come together on their own to build the thing--no instructions or person required.

14. The yellow thing that attaches to the beam is a protein that tells the beam to break apart and disassemble. Without it the beam would be a static, stable thing that could never be gotten rid of once built and the cell would die, not to mention not be able to move.

15. Self-assembly of the other main type of structural element, call it a rod ("microtubules"). Again, it's made like legos out of the same smaller protein over and over again.

16. Dis-assembly of the rods. This looks like a spontaneous process in the video--can't remember whether it is in real life or whether it's signaled.

17-18. Not only do the rods and beams give the cell structure, they also act as highways, allowing for the directed transport of cellular bits that need to go somewhere in particular. The pink thing ("kinesin") is the motor, like the cab of a big-rig truck, that binds to the rods and "walks" along them (If I remember correctly, there's very good evidence that they actually do walk like that!). The other side of the cab is attached to the load, just like the cargo part of the truck, which allows it to transport it down the highway. The giant blue sphere ("vesicle") is a bubble containing stuff that will eventually be pushed outside the cell. Think of it as the actual metal frame that's holding the stuff inside the truck, preventing it from spilling and keeping it together until it gets to the right place.

18. Wider view of the cell's innards, with many such cargo holds moving away from the nucleus (really big sphere in the background) towards the cell surface.

**For those who don't know, a quick summary of the "basic dogma" of molecular bio is: DNA contains hereditary info and resides in the nucleus. Think of it like a book. When the cell wants to make a particular protein, it generates a xerox copy of one line of the book (RNA string). The RNA string is processed and given a cap and a tail. The xerox string then leaves the nucleus and a code-reading machine ("ribosome") scans it in, decodes the message, and then spits out the protein that it codes for (most of the globs you've seen are protein). Knowing this will make it easier for me to describe the next section.**

19. Sudden zoom in to look at the outer surface of the cell's nucleus, inside which the DNA resides. The little white circles are pores through which only certain things, such as RNA, can pass. The stringy stuff going through the pores is RNA (xerox copy) that has been given a cap and a tail (the blobs on either end).

20. The RNA is now outside the nucleus and getting ready to be made into protein. Apparently the cap and tail come together (although this is the first I'd heard of it).

21. The green blob is half of the code-reading machine that will take the code in the RNA and match it up with the correct protein pieces to put together the whole protein. Once the other half comes on, it starts doing its decoding.

22. Zoom in on the code-breaker reading the xeroxed RNA string. The yellow stuff spewing out of the side is the newly-made protein that was coded for by the RNA. As it's being spit out, it is already starting to fold into the right configuration to work properly.

23. Once complete, the yellow protein goes off to do its job.

24. Two proteins are binding to each other, but I'm not sure why.

25. The code-breaker (ribosome) reading the xerox copy (RNA) of a different line of the book (gene in DNA) has read a signal in the code that says that the protein it's making is supposed to be sent to the outside of the cell (secreted) to signal to other cells. So instead of just making the protein where it is, it first moves to what I'll call the holding tank (ER). Think of the protein we're about to make as a baby dolphin, born in captivity on land but destined to be released into the ocean. The dolphin is a water creature, and its destination is water, so that's fine, but if it were just born on land and then dumped into the ocean, it would never survive to make it to the ocean. So instead, it's born in a tank of water that is located on land, allowing it to be in the proper environment for its entire life. Once it's ready, the whole tank is moved to the sea, and the tank is opened so that the water in the tank and the ocean can mingle, and the dolphin can seamlessly enter the sea. This is exactly what happens to proteins that are destined to be sent outside the cell. The environment out there is different from the environment inside the cell, and so they have to be put into a holding tank (the endoplasmic reticulum or ER) to make sure it stays healthy ("folds properly"). So the code-breaker and the xerox copy stay where they're comfortable, in the normal part of the cell, and they spit the new protein into the holding tank.

26. Even after the protein is made, it needs to have some accessories ("glycosylation," other modifications) put on to make it fully functional, so it needs to be transported to a second holding tank ("Golgi bodies") to get its bling attached. To get there, it's transported in a small tank, just as the dolphin would be. In this case, the tank is the same type of spherical bubble that we saw being transported along the highway in 17-18. These bubbles can also move without motors to get from one holding tank to another (the ER to the Golgi). In this clip, the small circles, or spheres, we see emerging from the flat surface are the transfer tanks leaving the first holding tank (ER) with proteins inside, bound for the second holding tank (Golgi).

27. Now we see the transfer tanks (vesicles) approaching the second holding tank (Golgi) from the bottom. It turns out that the second transfer tank is actually made of 3 independent tanks, which are the layers you see as you go up. Once the protein has made it through each of these, it is again put into a transfer tank (the spheres on the top of the screen going upwards) and this time can be sent to the surface to be pushed outside the cell.

28. We see a transfer tank (vesicle) similar to those that were leaving the last holding tank (Golgi) being carried up the rod (microtubule) highway by the truck (kinesin) towards the surface of the cell.

29. This is what happens when the transfer tank bubble fuses its membrane with the surface, sending its contents outside of the cell. The depression/hole is there because you're seeing one half of the inside of the sphere (which remember, is the same environment as the outside of the cell) as it fuses with the cell's membrane. The blue blobs are the contents of the transfer tank, which are being jetted out into the space between the macrophage and the blood vessel. Inside the cell are also molecules that are bound to the inner membrane of the tank (purple and yellow blobs). When the tank fuses with the outside, these proteins are now present on the outer membrane of the cell, ready to signal.

30-32. Close-up of the proteins that have just been put on the surface of the macrophage, as they aggregate and what looks like a lipid raft forms. They reach out and make contact with other proteins on the surface of the blood vessel, sending the signal to the macrophage to stop and leave the blood vessel.

33-34. Back to the cellular view. When the macrophage receives the signal, it stops rolling, and changes its shape entirely, spreading out across the blood vessel looking for a crack between the cells through which it can slip.

35. Back to the global view of red blood cells and macrophages in the vessel.