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Hank: Oh, hey! I didn't see you up there. How long have you been waiting in this line? I've been here for like 15 minutes, and it's frickin' freezing out here. I mean, whose banana you gotta peel to get into this club? Well, while we're here, I guess this might not be a bad time to continue our discussion about cells, because cells, like night clubs, have to be selectively permeable. They can only work if they let in the stuff that they need, and the kick out the stuff that they don't need, like trash, and ridiculously drunk people, and Justin Bieber fans, so no matter what stuff it is, it has to pass through the cell's membrane. Some things can pass really easily into cells, and without a lot of help, like water or oxygen, but a lot of other things that they need, like sugar or other nutrients or signaling molecules or steroids, well, they can't get in, or it will take a really long time for them to do it. Yeah, I can relate. (upbeat music with whistling) Today we're gonna be talking about how substances move through cell membranes, which is happening all the time, including right now in me and right now in you. And this is vital to all life, because it's not just how cells acquire what they need and get rid of what they don't. It's also how cells communicate with one another. Different materials have different ways of crossing the cell membrane, and there are basically 2 categories of ways. There's active transport and there's passive transport. Passive transport doesn't require any energy, which is great because important things like oxygen and water can use this to get into cells really easily, and they do this through what we call diffusion. Let's say I'm finally in this show, and I'm in this show with my brother, John. Some of you know my brother John, and I love him, but he, uh, he's not a big fan of people. I mean, he likes people, he doesn't like big crowds, being parts of big crowds with people standing nearby him, breathing on him, touching him accidentally, that sort of thing. Because John's with me at the show, we're hanging out with all of our friends near the stage, but then he starts moving further and further from the stage so he doesn't get a bunch of hipsters invading his space. That's basically what diffusion is. If everyone in the club were John Green, they would try and get as much space between all of them as possible until it was a uniform mass of John Greens throughout the club. When oxygen gets crowded, it finds places that are less crowded and moves into those spaces. When water gets crowded, it does the same thing. It moves to where there is less water. When water goes across a membrane, it's a kind of diffusion called osmosis. This is how your cells regulate their water content. Not only does this apply to water itself, which as we've discussed is the world's best solvent, you're gonna learn more about water in our water episode, it also works with water that contains dissolved materials or solutions, like solutions of salt water or solutions of sugar water, or booze, which is just a solution of ethanol and water. If the concentration of a solution is higher inside of a cell than it is outside of the cell, then that solution is called hypyertonic, like power thirst, it's got everything packed into it. And if the concentration inside of the cell is lower than outside of the cell, it's called hypotonic. Which is sort of a sad version of hypertonic. So, like with Charlie Sheen, we don't want the crazy, manic Charlie Sheen, and we don't like the super sad, depressed Charlie Sheen. We want the in-the-middle Charlie Sheen who can just make us laugh and be happy; and that is the state that water concentrations are constantly seeking, it's called isotonic when the concentration is the same on both sides, outside and in. And this works in real life, we can actually show it to you. This vase if full of fresh water, and we also have a sausage casing, which is actually made out of cellulose, and inside of that we have salt water. We've died it so that you can see it move through the casing, which is acting as our membrane. This time lapse shows how over a few hours, the salt water diffuses into the pure water. It'll keep diffusing until the concentration of salt in the water is the same inside the membrane as outside. When water does this, attempting to become isotonic, it's called moving across its concentration gradient. Most of my cells right now are bathed in a solution that has the same concentration as inside of them, and this is important. For example, if you took one of my red blood cells and put in a glass of pure water, it would be so hypertonic, so much stuff would be in the cell compared to outside the cell, that water would rush into the red blood cell, then it would literally explode. So, we don't want that. But if the concentration of my blood plasma were too high, all the water would rush out of my cell and it would shrivel up and be useless. And that's why your kidneys are constantly on the job regulating the concentration of your blood plasma to keep it isotonic. No, water can permeate a cell membrane without any help, but it's not actually particularly easy. As we discussed in the last episode, cell membranes are made out of phospholipids; and the phospholipid bilayer is hydrophilic, or water-loving on the outside, and hydrophobic, or water-hating, on the inside. So, water molecules have a hard time passing through these layers because they get stuck at the non-polar hydrophobic core. That is where the channel proteins come in. They allow passage of stuff like water and ions without using any energy. They straddle the width of the membrane, and inside they have channels that are hydrophilic, which draws the water through. The proteins that are specifically for channeling water are called aquaporins. Each one can pass 3 billion water molecules a second. Make me have to pee just thinking about it. Things like oxygen and water that cells need constantly, they can get into the cell without any energy necessary, but most chemicals, they use what's called active transport. This is especially useful if you want to move something in the opposite direction of it concentration gradient from low concentration to a high concentration. So, say we're back at that show, and I'm keeping company with John, who's being all anti-social in his polite and charming way, but after half a beer and an argument about who's the best Doctor Who, I want to get back to my friends across the crowded bar. So, I transport myself against the concentration gradient of humans, spending a lot of energy dodging stomping feet, throwing an elbow to get to them. That is high energy transport. In a cell, getting the energy necessary to do pretty much anything, including moving something the wrong direction across its concentration gradient, requires ATP. ATP, adenosine tri-phosphate. You just wanna replay that over and over again, until it just rolls off the tongue because it's one of the most important chemicals that you will ever, ever, ever hear about. Adenosine tri-phosphate. ATP. If our bodies were America, ATP would be credit cards. It's such an important form of information currency, that we're going to do an entire separate episode about it, which will be here. Ha, I was going in the wrong direction, but it will be here when we've done it. But for now, here's what you need to know. When a cell requires active transport it basically has to pay a fee, in the form of ATP, to a transport protein. A particularly important kind of frickin' sweet transport protein is called the sodium potassium pump. Most cells have them, but they're especially vital to cells that need lots of energy, like muscle cells and brain cells. (piano instrumental) Ah! (laughs) Biolography, (laughing) it's my favorite part of the show. The sodium potassium pump was discovered in the 1950s by a Danish medical doctor named Jens Christian Skou, who was studying how anesthetics work on membranes. He noticed that there was a protein in cell membranes that could pump sodium out of a cell; and the way he got to know this pump was by studying the nerves of crabs, because crab nerves are huge compared to humans' nerves, and are easier to dissect and observe. But crabs are still small, so he need a lot of them. He struck a deal with a local fisherman, and over the years, studied approximately 25,000 crabs, each of which he boiled to study their fresh nerve fibers. He published his findings on the sodium potassium pump in 1957, and in the meantime became known for the distinct odor that filled the halls of the department of physiology at the university where he worked. 40 years after making his discovery, Sku was awarded the Nobel Prize in chemistry. And here's what he taught us. Turns out, these pumps work against 2 gradients at the same time. 1 is the concentration gradient, and the other is the electric chemical gradient. That's the difference in electrical charge on either side of a cell's membrane. So, then our cells that Sku was studying, like nerve cells in your brain, typically have a negative charge inside relative to the outside. They also usually have a low concentration of sodium ions inside. The pump works against both of these conditions, collecting 3 positively charged sodium ions, and pushing them out into the positively charged sodium ion-rich environment. To get the energy to do this, the protein pump breaks up a molecule of ATP. ATP, adenosine tri-phopsphate, an adenosine molecule with 3 phosphate groups attached to it. So, when ATP connects with a protein pump, and enzyme breaks the covalent bond on one of those phophtaes in a bust of excitement and energy. The split releases enough energy to change the shape of the pump so that it opens outward and releases 3 sodium ions. This new shape also makes it a good fit for potassium ions that are outside the cell, so the pump lets 2 of those in. So, what you end up with is a nerve cell that is literally and metaphorically charged. It has all those sodium ions waiting outside with this intense desire to get inside of the cell, and when something triggers the nerve cell, it lets all of those in. And that gives the nerve cell a bunch of electric chemical energy, which you can then use to help you feel things or touch or smell or taste or have a thought. There is still yet another way that stuff gets inside of cells, and this also requires energy, it's also a form of active transport. It's called vesicular transport, and the heavy lifting is done by vesicles, which are tiny sacs made of phohpholipids, just like the cell membrane. This kind of active transport is also called cytosis, from the Greek for cell action. When vesicles transport materials outside of a cell, it's called exocytosis, or outside cell action. A great example of this is going on in your brain right now, it's how your nerve cells release neurotransmitters. You've heard of neurotransmitters, they are very important in helping you feel different ways; they're like dopamine and serotonin. After neurotransmitters are synthesized and packaged into vesicles, they're transported until the vesicle reaches the membrane. When that happens, the 2 bilayers rearrange so that they fuse, and then the neurotransmitter spills out, and now I remember where I left my keys! Now, just play that process in reverse and you'll see how material gets inside the cell, and that's endocytosis. There are 3 different ways that this happens. My personal favorite is phagocytosis. And the awesome there begins with the fact that that name itself means means devouring cell action. Check this out. So, this particle outside here is some kind of dangerous bacterium in your body, and this is a white blood cell. Chemical receptors on the blood cell membrane detect this punk invader and attach to it. Actually, reaching out around and engulfing it. Then the membrane forms a vesicle to carry it inside where it lays a total unholy beat down on it with enzymes and other cool weapons. Pinocytosis, or drinking action, is very similar to phagocytosis, except instead of surrounding whole particles, it just surrounds things that have already been dissolved. Here the membrane just folds in a little to form the beginning of a channel, and then pinches off to form a vesicle that holds the fluid. Most of your cells are doing this right now, because it's how our cells absorb nutrients. But what if a cell needs something that only occurs in very small concentrations? That's when cells use clusters of specialized receptor proteins in the membrane, that form a vesicle when receptors connect with the molecule that they're looking for. For example, your cells have specialized cholesterol receptors that allow you to absorb cholesterol. If those receptors don't work, which can happen with some genetic conditions, cholesterol is left to float around in your blood and eventually causes heart disease. So, that's just one of many reasons to appreciate what's called receptor mediated endocytosis.