# biological membrane **Channel:** M A **Source:** https://www.youtube.com/watch?v=SE8hgYRRyi4 **Transcript page:** https://www.withtranscript.ai/video/SE8hgYRRyi4 ## Chapters - 0:00 — Membrane Basics and Water Interactions - 10:54 — Phospholipids Build the Bilayer - 23:58 — Vesicles and Membrane Fluidity - 27:51 — Membrane Proteins and Cancer Signaling - 34:05 — Lateral Diffusion and Glycocalyx ## Transcript **[0:00] Speaker A:** Hi everybody, let's get started. Today we are going to talk about biological membranes. **[0:13] Speaker A:** All cell life has a cell membrane that separates the chaos outside the cell with high degree of organization within the cell. Cell membranes regulate the flow of nutrients and waste that enter and leave the cell. The cell membrane surrounds the cytoplasm of living cells, physically separating the intracellular components from the extra- cellular environment. **[0:56] Speaker B:** Between the living machinery of the inner cell and the harsh conditions of the outside world stands the cell's plasma membrane. As crucial as this barrier is, it's surprisingly flexible. Push it and watch it move. Poke hard enough and it might break and begin to regroup. The lipid molecules of the membrane naturally assemble in a double layer because their tails repel water as their heads **[1:27] Speaker A:** attracted. So what are the main functions of cell membrane? First, to separate the inside of the cell from the outside environment, to be protective in such a way. Cell membrane provides a surface on which chemical reaction take place, which is receptors that actually have their enzymatic reaction just on the lower leaflet of the plasma membrane, and also regulates the passage of material into or out of the cell. Well, the plasma membrane allows cell recognition. **[2:23] Speaker A:** We have interactions between different cells, and those interactions are very important for the activity of the cell. In cancer, metastasis is when this interaction is not so strong. The structure of the membrane must separate between 2 watery compartments. So if this is a cell membrane that covers a cell, we have water outside the cell and water inside the cell. And the physical structure of the membrane needs to separate between those compartments. **[3:24] Speaker A:** So what you see here is a water molecule, H2O, 2 H and O, oxygen. So, if I have a water molecule, I have some negative charge over here and a little bit of positive charge over here and here. Now, let's look at 2 molecules of water together. Suppose I have another water molecule over here and one here. So I have a little of— a bit of negative charge from this one over here and a bit of positive charge from the other molecule over there. **[4:28] Speaker A:** Not that much. But I got some positive and negative charges. It's like a magnet, which also have positive end and negative end. So the negative and the positive can have some interactions in between them. So water molecules are related to each other in some ways. **[5:14] Speaker A:** So again, I found a really nice animation in another online course by Professor Jon Gershoni from Tel Aviv University. So let's use this. I think that it's going to give us quite a bit of interesting information here. So here again, we have one molecule of water. And actually, it's going to have some interaction between the negative part of the oxygen and the positive part of the hydrogen over here. **[5:56] Speaker A:** Now, you know, when you have a magnet, that's not the only option that you can use 2 magnets. Magnets can attract or repel. I mean, for example, if you put negative to negative, if magnet They are going to repel each other. But energetically, those magnets are going to be settled when they attract to each other. That's going to be the best energetically situation for magnets, and that's exactly what we can see here. **[6:42] Speaker A:** With water as well. They prefer actually to be in the position that the positive and the negative are interacting with each other by forming hydrogen bond. So again, this is just 2 little molecules of water. Each with tiny attraction forces. But when I have a big cup of water, well, here the entire system is going to be arranged in such a way. **[7:27] Speaker A:** The water molecules are going to interact with other water molecules by hydrogen bonding. So those are very weak interactions, like, you know, very little magnets, that this interaction is based on hydrogen bonds, which are weak bonds. But they are going to be settled in such a way Because it is energetically favorable. That's the way that they are going to be settled. **[8:16] Speaker A:** So if you use other polar molecules such as acetone and you put it inside the water you are actually going to have the same— they are going— the acetone is going to participate with those type of interactions. They are actually going to be dissolved in the water, to be part of the water. So, uh, but suppose that you are taking non- molecules such as fatty acids, and you put those molecules into highly structured cage of water, when they get there, they act like an elephant in a china shop. It's going to disrupt the hydrogen bonds, that the water molecules would like to make with each other. So how the system can react to this? Well, I mean, I'm sure that you know. I mean, water and oil cannot be mixed. Water molecules would all like to be communicating with each other, hydrogen bonding with each other, right? **[9:56] Speaker A:** And they would like to push out those nonpolar molecules. So what's going to happen? **[10:07] Speaker A:** Well, they are going to separate. Oil and water cannot be mixed. And that's because the nonpolar molecule cannot hydrogen bond. All right, so you know enough that we can now start applying all those type of information in order to understand a bit better the way that membranes are structured in order to separate between 2 watery compartments. **[10:54] Speaker A:** So the structure of phospholipids is responsible for the basic function of membrane as barriers between 2 polar watery compartments. So let's start with this structure. So let's start with acetic acid. Well, acetic acid is polar and can be dissolved in water. You know, acetic acid is actually the vinegar that you put in your salad. And it is dissolved very, very nicely in the water of your— that you probably have in your salad. **[11:49] Speaker A:** So we are talking here about a molecule which is polar and again can be dissolved in water. That's actually important. It can form bonds with water in a similar way that water molecules are interacting with each other. So this is hydrophilic. Now let's try to add to this hydrophilic molecule hydrophobic. **[12:28] Speaker A:** Molecules. So, so this is acetic acid, vinegar, yes, as I mentioned. And now we are going to add CH3, which obviously cannot form hydrogen bonds. It is hydrophobic. **[12:54] Speaker A:** So here you have a tail, and this tail can be quite long. So what you have right now over here is an acidic group, and on the same molecule you also have hydrophobic tail. So what we call this is a fatty acid. This is fatty acid. And when you are using 2 fatty acids linked together, what you have is lipid. So we have hydrophilic and hydrophobic tails. And if you add phosphate, you are making this hydrophilic head to be even more hydrophilic. **[13:58] Speaker A:** So that's what we call phospholipids. Lipids, which is phosphorylated, and phospholipids are amphipathic. Amphipathic means that they have 2 different chemical characters. The one character is hydrophilic and the other one is hydrophobic. **[14:31] Speaker A:** So the phospholipids are amphipathic in that they have hydrophilic phosphate-containing head and very hydrophobic tail. So the phospholipids interact with water, they arrange themselves so that their polar head have a contact with the water molecule and their hydrophobic tails move away from the water. Think about it. The best geometry to satisfy both characters is to form a bilayer of phospholipids when the head have a contact with the water, while the tails mingle themselves among themselves, which are actually interacting between each other by hydrophobic bonds. And that's going to make the lipid bilayer a biological membrane. So that's actually the fundamental structure of all biological membranes that are surrounding cells. Inside the cell, the membrane can further divide into subcellular compartments which are called So the membranes that we have are not just membrane that are— is covering the cell, but actually all the endoplasmic reticulum, the all other membrane-bound, the organelles are actually using the very same principle. **[16:46] Speaker A:** Mitochondria, lysosomes, just name it. All of them are made out of biological membranes, and those biological membranes are actually helping us to have an extra compartment with different chemical composition. Mitochondria can do quite a lot of things, among other things, to make energy, ATP, and the lysosomes are going to help us to recycle things in the cell, etc. Okay, let's go once again to see this from maybe different direction. Again, what we have is the hydrophilic head actually by itself, it's negatively and positively charged. So the negative charge, it's coming from the phosphate group. Positive charge, it's coming from a nitrogen So again, water— if we will just take the head, you're going to see that water can interact through the negative charge of the oxygen with the positive part of the head, and vice versa for the phosphate group. Where the hydrogen, positively charged, is going to bind to them. **[18:41] Speaker A:** So you can have quite a lot of molecules of water which can cover the head, and actually that's the reason that we call this head hydrophilic. It's like water, it really likes to bind to water. On the other hand, those hydrophobic tails are not going to interact with water. They don't have the ability for hydrogen bonding, and they're going to be moved as far as possible from the water. **[19:29] Speaker A:** Molecules. So again, just to make it clear, what you see here is phospholipids bilayer. Again, it's made with a lot of phospholipids that are must to cover the The cell cannot have holes. It must be covered entirely with a membrane. And if we are looking further into this, you can see that the tail, the hydrophobic tail, needs to interact with each other, and they are So hydrophilic heads, hydrophobic fatty acid tails, and this type of molecule is amphipathic. **[20:29] Speaker A:** They have hydrophilic and hydrophobic parts. So phospholipids are amphipathic molecules. Membranes are actually developed spontaneously. You just need to put phospholipids in water and after some time the membrane is going to be developed by itself. You don't need here not enzymatic activity, not specific carriers or anything. **[21:04] Speaker A:** This is simply based on the characters of the phospholipids. So the head group is polar and hydrophilic, so it is associated with water from both sides of the membrane, and that's going to take place spontaneously. As long as you have those molecules with water, they're going to find their best position After all, the long tail is nonpolar and hydrophobic, which is repelled by water. **[21:55] Speaker A:** So the hydrophobic portion of 2 molecules or more tend to associate with each other as well. We call them hydrophobic bonds. I mean, lipophilic, lipid lover, hydrophobic bonds. That's actually going to add some extra way for the phospholipids to be stabilized. So what you have is the following. **[22:36] Speaker A:** First, you have the powers which are holding the phospholipids in place because of hydrophilic connections with water. So the tails is going to be repelled from the water, the head is going to be attracted by the water. And by itself, that's what you're supposed to get simply by this specific force. But this system is going to be stabilized even further by those hydrophobic bonds between the different hydrophobic tails. So you have 3 different powers to stabilize the phospholipid bilayer. 2 are repelling and attractions by the water, and second, the fact that hydrophobic tails like to bind to other hydrophobic tails. **[23:58] Speaker A:** Vesicles are very commonly used. So again, I mean, how this system is working— this system is working is by fusion between the vesicle and the larger membrane. So the vesicle have an ability by the help of other proteins, we'll talk about it quite a lot, to be fused with the larger membrane, like the plasma membrane. And by doing so, everything that it was in the vesicle and inside the cell is going to be outside of the cell. **[24:44] Speaker A:** And vice versa. Let's say that you want to use an artificial vesicle and to fill it up with some drugs. So when you are using the vesicle from the outside, it can be fused with the plasma membrane and the drug can be moved inside this— to the inside of the cell. So naturally vesicles are formed in the cell all the time and they help to move chemicals outside or inside of the cell. And again, we are going to speak about this quite a lot. **[25:35] Speaker A:** So vesicle is a pocket in made of membrane that is separated from the cytoplasm of the cell, a carrier of molecule in and out of the cell without crossing the membrane directly. But the fusion actually put whatever in the vesicle on the other side of the membrane. **[26:09] Speaker A:** So, uh, what else we can say about the plasma membrane? Well, it's a flexible barrier, and the bilayer of naturally occurring phospholipids are flexible. They're kind of jello-ish type of material. They're not solid. **[26:36] Speaker A:** So, uh, **[26:37] Speaker C:** to demonstrate the fluidity of the lipid bilayer, a piece of the plasma membrane of this neuronal cell is pulled out with laser tweezers. **[26:51] Speaker C:** Remarkably, moving this membrane tubule rapidly back and forth Does not rupture the plasma membrane, which flows quickly to adapt to the mechanical distortion. **[27:15] Speaker A:** Okay, so the fluidity of A lipid bilayer is critical for its function. You do not want it as a solid material. Also, you don't want it— the membrane to be totally watery. You need it to be something in between. Again, jellyish type of material. **[27:51] Speaker A:** Transmembrane proteins. Again, the biological membrane is full with a lot of different proteins. Some of them are enzymes, that the enzymatic activity can be found inside the cell. They can act like receptors, means they can recognize something outside and can react inside the cell. Others may act like channels or pumps or other options. **[28:31] Speaker A:** So when it comes to transmembrane proteins, they have many different functions. They can be transport proteins, and I mentioned some of them already. They can participate in cell-cell recognition. Cells need to really know what are— who are their neighbors. Sometimes it's maybe the same cell, sometimes maybe it's not, and cells are working in coordination. **[29:08] Speaker A:** Between themselves and their neighbors. So they need to have some ability to be recognized and to recognize other cells. So different cell types have different set of membrane proteins that can be recognized. Signal transduction is actually based on the idea that the receptor can recognize something like this ligand, and then the enzyme inside the cell— the enzymatic activity of this protein inside the cell is going to react to this type of interaction. So again, the receptor can recognize a ligand, and this interaction— again, we'll talk about tyrosine kinases and it would be much more specific than this— is going to induce specific activity, enzymatic activity, inside the cells. So the receptors serve as sensors. Through which the cell receives signals from their environment and reacts accordingly inside the cell. So, well, I mean, normally that's something good. We want to have those type of abilities. **[30:45] Speaker A:** But actually cancer cells know how to use those type of activities in a totally negative way. For example, if you have an enzyme that's going to send a message to the cell, start cell division, cancer cells are going to take advantage of this receptor and making the signal to go to the cell all the time, as much as possible. And they are doing it with different tricks that— and I want to speak with you right now about one of them, which is called HER2. HER2 is a receptor that sends the signal to the cell to divide, and cancer cells are using it in a very unique way. So HER2 can recognize a ligand and can react inside the cell. Now, in cancer cells, what you have is a lot of HER2. I mean, the gene for HER2 is amplified 20 times fold, and you are going to have many, many more molecules of receptors on the surface of the cell, and those molecules can actually be very, very sensitive to the ligand and send a lot of messages to the cell to replicate. **[32:26] Speaker A:** And that's not so great because, you know, that's really about the development of cancer. **[32:36] Speaker A:** So, how to deal with this? Actually, scientists discovered that they can block this receptor by an antibody that actually it's a biological drug, which is actually antibody, and this is a drug called Herceptin. Now, those antibodies can bind to the receptor specifically, and when the ligand is there to interact with this receptor, well, I mean, the antibodies are going to block the ligand from interacting with the receptor. As the result of this, the receptor is not going to send the bad message to the cell to replicate. Because what cancer cells are going to do when they are going at once to lose their receptor that makes the cells to replicate, I mean, they are going to be highly confused. **[33:46] Speaker A:** And what cells are doing when they are highly confused, they are killing themselves. So cells that have this abnormality are going to kill themselves simply because the drugs make them to be confused. **[34:05] Speaker A:** Both proteins and lipids as well are able to diffuse laterally throughout the membrane. And again, I mean, this protein, for example, cannot go out because the nonpolar region is going to hit water. So it's going to be back, cannot really go down for the same reasons. **[34:31] Speaker A:** But laterally, that's not a problem because the nonpolar, when it is here, if it's going to be here, it's still going to be at the same type of environment. So that's why the protein can go laterally and receptor tyrosine— receptors in general are using this type of activity quite a lot. **[35:00] Speaker A:** Most of the proteins that are exposed outside of the cell are likely to be glycosylated. So most transmembrane proteins of the plasma membrane are glycoproteins with their oligosaccharides exposed on the surface of the cell. So the role of the sugars that we call them glycocalyx is to protect the cell surface and to serve as markers for variety of cell-cell interactions. So most transmembrane proteins in animal cells are glycosylated. The oligosaccharide chains are actually always present in the non-cytosolic side of the membrane. When you have sugars, it's not in the cytosol. Consequently, the surface of cells is covered by carbohydrate coat formed by the oligosaccharides and glycolipids as well, and the transmembrane glycoproteins.