The Lipid Bilayer: Study with Video Lessons, Practice Problems & Examples

The lipid bilayer, essential for cell membranes, consists of amphipathic molecules like phospholipids, sphingolipids, and glycolipids, which create a hydrophobic core and hydrophilic surfaces. Its fluidity is influenced by lipid composition, including chain length and saturation, with cholesterol playing a key role in maintaining membrane stability. The bilayer is asymmetrical, with distinct cytosolic and extracellular faces, and is formed in the endoplasmic reticulum (ER) through specific enzymes like scramblases and flipases, ensuring proper lipid distribution and functionality.

Types of Lipids

Hello, everyone. In this lesson, we are going to be talking about the lipid bilayer and the different types of molecules that are going to come together to form the outside of our cells. Okay. So the lipid bilayer, obviously, is going to be the outer membrane of our cells that allows our cells to take in certain materials or get rid of certain materials, and it protects our cells from the outside world. Now, membrane lipids are going to be composed of a combination of a whole bunch of different things, and they're going to be composed of a combination of non-polar tails and polar head groups. In general, this is going to be how the molecules of the lipid bilayer are going to be created. They're generally going to have non-polar or hydrophobic tails, and they're going to have polar or hydrophilic head groups. This is going to allow the lipid bilayer to have an internal hydrophobic layer and external hydrophilic layers, which give it its unique properties. Now, many molecules that build or make up the lipid bilayer are going to be amphipathic. These are going to be things like certain types of lipids inside of the membrane. Also, membrane proteins, especially transmembrane proteins, are going to be amphipathic. They are going to have a hydrophobic portion and a hydrophilic portion as previously discussed. They are going to have two different characteristics inside of the same molecule to give the lipid bilayer its unique characteristics. So now let's talk about some of the different types of lipids that you're going to find in the lipid bilayer because, well, we obviously have to have lipids in there because it is the lipid bilayer. The first one is probably going to be the most famous, the most recognizable of all the lipids, the phospholipid. I'm pretty sure you guys have heard of this before. But just remember that the phospholipid is the most common lipid found in the membranes of the cell, including the lipid bilayer and all those little vesicles and different types of membranes inside of the cell as well. They are going to have a hydrophobic tail and a hydrophilic head, as discussed above. They are going to make up the bulk of this membrane. They are the foundation of this membrane. Everything else is pretty much going to build off of these. These are the building blocks for the rest of the membrane. Now, there can be different types of phospholipids. Generally, when we talk about phospholipids, we don't always talk about the different types. We just talk about them in general, but there are going to be different types, and this is going to be based on the composition of their head group. Remember, they have a hydrophilic head group. You can have different types of molecules in that head group, which will give them unique properties and their unique name. Some examples are right here. But there's a whole bunch of different types of phospholipids that we're not really going to get into. I'll show you a picture of some down below, but we're not going to go into all those specific types. Just know that they exist. Okay. So, the next type will be the sphingolipids, which have a pretty cool name. They will contain a sphingosine, which will have an amino alcohol with a long hydrocarbon tail linked to a fatty acid. Basically, they are just another specialized type of lipid that exists inside of the lipid bilayer. Again, similar to the phospholipids, the composition of their attached groups give them their unique names. Some examples are going to be right here. What do these guys actually do? Researcher's believe these help protect our cells, protect the inside of our cells by maintaining the stability of the lipid bilayer and protecting the cell from foreign objects or environmental factors, by not allowing those things into the cell. So basically, they're scattered around the lipid bilayer, and they function as part of the lipid bilayer and maintain that stability. Some of them, because of their unique properties, can be classified as phospholipids, but not all of them. Okay? Alright. So now, let's move on to glycolipids. Glycolipids are quite interesting. These will be lipids that are attached to a carbohydrate or a sugar group. Right? There are many different types of glycolipids, as we can see here. Again, their uniqueness, their unique names, their unique properties generally come from the sugar that is attached to the lipids. Now, what do glycolipids do? They're scattered around the cell membrane. What do they do? They're generally used for cell-to-cell recognition. How do cells recognize each other? Generally, glycolipids are placed in the cell membrane, and they act like a name tag or a banner saying I am a red blood cell that's type A. Glycolipids are going to be utilized to tell which types of blood cells you actually have. So your blood cell type is going to be indicated by your glycolipids, whatever type of glycolipid you have. Usually, these are going to be utilized for cell recognition and cell type identification. Okay. So we also have sterols. Sterols are steroids that have a hydroxyl group attached to them and a short hydrocarbon chain, and generally, they're going to be quite rigid. One of the most famous examples of a sterol will be cholesterol. We've all heard of cholesterol before. Usually, when you think of cholesterol, you think it's not a good thing. There's bad cholesterol, and there's good cholesterol. Cholesterol is very important in animal cells. What does it do? It is going to allow the fluidness, the fluid capacities of the cell membrane. Now, you may be thinking, wait a minute. You just told me that these sterols are very rigid. They are very rigid. How does this actually lead to the cell being more fluid-like? Well, these cholesterol molecules are going to be placed at different areas inside of the cell membrane, and basically, it ensures that the cell membrane stays fluid even when it's really cold, or it stays strong and solid even when it's really hot, and maybe that fluid membrane wants to melt away. Those cholesterol molecules are going to ensure that it doesn't do that. Basically, these cholesterol molecules are utilized to keep the fluidity of the cell membrane at a normal equilibrium point. You can actually add cholesterol to your cell membrane, and you can take it away depending on the temperature that the cell is experiencing. At normal temperature, around 30% of your cell membranes are going to be cholesterol, but that can change depending on the temperature. Okay. So now, let's look at our examples. These are just some examples of the different types of phospholipids. Usually, when we talk about phospholipids, we don't talk about all the different types, but here are some interesting types, and they're all going to be unique in one location, and that's going to be the head, or the hydrophilic head portion of the phospholipids. This is where they're going to get their unique names based on the characteristics of the molecules and the atoms that make up the hydrophilic head of the phospholipids. If you guys were curious, this is what cholesterol looks like. It's a pretty rigid molecule that your cell puts into your membranes and takes out of your membranes depending on what it needs. Okay, everyone. I hope that was a great overview of the different types of lipids that you're going to find in your lipid bilayer. Let's move on to our next topic.

Bilayer Composition and Asymmetry

Okay. So now we're going to talk about bilayer formation and fluidity. The important thing you need to know is that lipid bilayers are fluid. I feel like a lot of times when people are studying the cell, they kind of think of it how you see it in the picture in your textbook, just sort of this 2D structure that's just sitting there and stuck in place, but that's not the case at all. Everything in the cell is moving, especially the lipid bilayer. Lipids form this super highly flexible lipid bilayer when they're put into water. So if we just have a bunch of individual lipids and we just throw them into water, it's actually the most energetically favorable conformation. Meaning that if we have these lipids, these individual lipids, and we just throw them all in a bathtub, they're going to form a lipid bilayer. We don't need enzymes for it. We don't need anything else guiding the process. If you just throw them in together, they'll automatically form a lipid bilayer because it requires no energy to do so. Right? Like, they just form it, and they like being that way. It takes energy to actually separate the bilayer, not form it. So because it doesn't require any energy and they want to be in that conformation, when you throw lipids together, they form a lipid bilayer. This is actually super important because if you just have all these lipids and you throw them in water, they form this bilayer.

What you can do is you can actually form the self-sealing compartment. So, what do I mean by that? Well, like a cell, for instance, a cell exists in lots of different environments. There are bacteria that live in water, and it's just surrounded by water. But the bacteria itself is not affected by that water because the lipids have sealed all of its bacterial insides inside the bilayer. Because lipids self-seal, they automatically form that. And if something disrupts it, say that bacteria gets poked with something, and it disrupts that bilayer, the bilayer just goes and fixes it automatically. It just comes back together. One of the examples that you'll often hear when discussing the lipid bilayer is using golf balls in a bathtub. You can imagine that if you have a bathtub, it's half filled with water, and you throw a bunch of golf balls in it, they're going to evenly distribute out across the bathtub. What we mean by self-sealing is if I were to just jump into the bathtub, I would create this huge break between the golf balls. Because my body is separating the golf balls apart. But if I were to remove myself from the bathtub, those golf balls will come back together because there's so many of them, they self-seal. Lipids are the same way. If you have a lipid on a bilayer of a cell and it gets poked or wounded or damaged in some way, it'll come back together, self-seals. So they spontaneously form and they can reform if something tears them apart. This is really important mainly because it forms a boundary. It separates what's inside the cell versus what's outside the cell, and that is what allows us to live. That is really the most basic thing we need to live. We have to be able to separate ourselves from the outside world, and even the smallest, most simple bacteria can do that because they have a lipid bilayer that separates themselves, forms that boundary, and does that without any energy and self-seals if it were to be damaged. This is super, super important, for understanding biology, but also understanding evolution, because this is one of the very first things that had to evolve to create life is the ability to separate what could potentially become living in the future to the external environment. So, the lipid bilayer is super important.

Now we're going to go back to that bathtub model with the golf balls. This model is actually called the fluid mosaic model, not with the golf balls, but with the lipids. The fluid mosaic model describes the nature of membranes, and what that means is that it just describes the fact that the lipid bilayer is moving around. It's fluid. It's not stuck in place. The lipids don't just bind to each other and just sit there rigid. They're moving around like golf balls would in a bathtub if you filled them up. They potentially could spin, they would switch places with one another, and they would just move all around the bathtub, and lipids do the same on a cell membrane. There are 3 types of movement that you need to know about. We have lateral movement, rotational movement, and transverse movement, or you can call this diffusion. Typically in your book, it's called diffusion, but another term for it, the simplified version of it, is how the lipids are moving.

In lateral diffusion, what it means is the movement of individual lipids in a single bilayer sort of switch places. What you would need to know about this is if you have 2 golf balls next to each other in the bathtub, and then all of a sudden, they're moving, they're moving, and then they switch places. So, it's just moving, you know, across the surface of the bathtub for the golf ball, so it's sort of moving laterally or moving across the surface. Rotational diffusion is a single lipid, an individual lipid, and it's when it's rotating. So you can imagine that that golf ball is just spinning in place. We'll think rotational is spinning in place, and it actually in lipids mean golf balls aren't going to move this fast, but lipids in a bilayer can actually move super fast up to 500 spins a second. So golf balls in a bathtub are not going to do that, but lipids can, and that's super fast.

Then the final one is transverse diffusion, and this is the most rare. What would happen is if that golf ball decided to traverse the bathtub and go to the bottom of the tub and just sit there at the bottom. Now you can imagine that's going to be a super rare movement, and it also is for lipids. Lipids usually don't just decide to flip to the other side of the membrane, but they can. So if I were to describe this, I would flip to another side. And so, like I said here, it's extremely rare, but they can do it. Now, studying this movement has become very difficult for scientists, but if you were a scientist, you're interested in studying this, one of the things you would need to know is that liposomes are made in a laboratory, so synthetically made. They're made by scientists and they're like lipid balls essentially, and they're used to study how lipids move in a membrane. Liposomes are how scientists have figured out these three different types of movements. Here's an example of a bilayer. We have our lateral diffusion where if this red lipid here is moving across the surface to this other place. We have rotational diffusion, where this individual single lipid is rotating in place. And then, we have the most rare type, the most rare type, which is reverse diffusion, where this blue lipid here just, for some reason, decided to go to the other side of the membrane and ended up over here. So, lipids move, they form boundaries, they self-seal, and these are the three types of movements that lipids can do in a membrane and they move a lot and they're always moving. So, it's important to know lipids move. They're fluid. So, with that, let's move on.

Bilayer Formation and Fluidity

Okay, so in this video, we're going to talk about bilayer composition and asymmetry. So, what that means is we're going to discuss what the bilayer is made of, its composition, and the fact that it's not symmetrical, meaning that each side of the bilayer is different, having different components. So first, let's talk about composition. The composition, what the membrane is made up of, the type of lipids in the membrane, are really important because they affect how fluid the membrane is, meaning how much it can move around, and then what it can do, its function. The fluidity of the membrane, its movement, is controlled by not only the amount of lipids, how many lipids are in it, but also by the type. Certain types of lipids make it more fluid and other types make it less fluid. Some examples of aspects that make it more fluid are shorter chains, the shorter hydrophobic chains. The average is around 18 to 20 carbon chains in a lipid. But if you have shorter than that, say, 14, for instance, which it can go down to, then that's going to make the lipid more fluid; it will be moving around more. If you want a membrane that's less fluid, you can make the hydrocarbon chains longer, right? Exactly. But there's a second thing that you can do, and that is saturated hydrocarbon chains. So, what does it mean to be saturated? You go over this in chemistry. Well, saturation has to do with the number of double bonds, and saturated hydrophobic chains have no double bonds. So, those without any double bonds, that means they're all single bonds, and that means they're saturated, and if they're saturated, they are more rigid. And so that's going to make the membrane less fluid. Whereas, unsaturated, which have double bonds, are more fluid. So, what are some aspects that make it more fluid? It's unsaturated bonds, it's shorter chains. Those types of things make the lipids in the membrane more fluid. And so, another way— that's sort of the composition, different types of features that lipids can have, but remember, it's also the type of lipids in the membrane that can also affect fluidity, and a big example of this is cholesterol, and cholesterol can significantly affect membrane fluidity. What it does is, cholesterol is a short, rigid molecule. And whenever it integrates into the membrane, it also makes the membrane more rigid. So it's short, it's rigid, and it sort of sinks into the lipid membrane, and that makes it less fluid. So, the membrane's less fluid, less permeable, and cholesterol is a very common method by which membranes adjust their fluidity, so they add more cholesterol if they want to be less fluid, or they remove it from the membranes if they want to be more fluid. And it makes up about 20% of the weight of lipids in animal cells, including our cells as well. So, here we have saturation of lipid hydrophobic chains. Remember saturation equals no double bonds, and unsaturated equals at least one double bond. This one is monounsaturated, meaning it has one double bond in it right here. And you can see that when you add a double bond into this lipid, it creates a little kink, right here, where the lipid tails or those hydrophobic tails are no longer perfectly aligned with each other. They separate out from each other. And when they do, that means that when they insert into the membrane, you have this extra space here, right? There's all this extra space, and what this means is this extra space makes it more fluid. Whereas, when you're tightly packed, as in saturated lipids, it's going to be less fluid because everything's tightly packed together. So that is the composition, but now let's talk about asymmetry because there are all these different lipids, right? There are different lipids of length, lipids of saturation versus unsaturation, different types of lipids, like cholesterol, and such. And the position of these elements in the membrane is not equally distributed on each side. So, what that means is that one side of the membrane bilayer and the other can be different. One side can contain more cholesterol, the other can contain more double bonds, more unsaturated hydrophobic tails. It just means that they're not equal. The two sides of the membrane do not look alike. They're not symmetrical. We call them asymmetric. And because they're not alike, we have to differentiate them. It's not that we can just say, oh, that's a bilayer; all the lipids are the same, et cetera. No, they're different, so we have to give them different names. So, we call them either the cytosolic phase or the extracellular phase. The cytosolic phase is going to face the cytosol, right? That makes sense. The extracellular face is going to face the extracellular environment. But sometimes we call this the luminal face because it can either face the extracellular environment, so outside the cell, or it can face inside a lumen. So, for instance, if we have a membrane here, this would be the extracellular face, and this would be the cytosolic face. But if we had a vesicle, right, so here's a circle, this would be the luminal face of the membrane facing inside the vesicle, facing inside the lumen of the vesicle, and this would be the cytosolic phase because now we're in a vesicle, we're inside the cell, so that outer membrane is still facing the cytosol. So, those are the two terms we use to name lipids. Now, there are some enzymes that we need to know about. It's not just lipids in the bilayer; there are also enzymes. So, the first one is flippases. Now, what do flippases do? Well, they flip lipids to the other side. And so, flippases are important because they're very specific. They don't just move random lipids. They aren't just these enzymes coming up the bilayers and flipping whatever they want willy-nilly. No, they take specific lipids, and they flip them to the other side, and generally, these enzymes are in the ER and the Golgi, which is where lipid synthesis really takes place and forms in the cell, and so flippases are really responsible for making that asymmetry, right? Because if it was just random, it's likely that some elements would be on one side, some on the other, but flippases, they say, no. This is going to be asymmetrical, and it's going to be exactly how I want it to be. So, they target specific lipids and move them to the correct side of the bilayer that they are supposed to be in. Another enzyme you need to know about is phospholipases, and what these are, they're enzymes; they break bonds, and they are only found on the cytosolic side. So, that means that lipids on the cytosolic side are going to be exposed to these phospholipases. These phospholipases are coming in; they're breaking bonds between lipid molecules, and what that does is it can change the structure, it can change the fluidity, and it just causes that one side, the cytosolic side of the membrane, to be different from the other side of the membrane. And then, finally, we'll talk about lipid rafts. And we might mention these again when we talk more about membrane proteins, but lipid rafts are sections of the membrane that are called functional domains, meaning that they're kind of different from the rest of the surrounding membrane. They have certain proteins. They have certain lipids in them, and usually, those lipid rafts have some kind of function. So, they collect a bunch of lipids that maybe do the same thing. And so, that little section of the membrane is a lipid raft, and it has a particular function, and that function can be a lot of different things. So, let's look at an example of a lipid raft. So, we have our bilayer here. Here's a lipid raft where these proteins have accumulated these similar proteins but also different types of lipids. So, this bright green thing here is cholesterol, and this section has a lot more cholesterol than other sections of the bilayer. And so, this lipid raft is going to have some kind of function. It looks, in this case, it's a transmembrane protein, so it's probably going to be transporting things across the membrane. And the cholesterol is going to add that rigidity to that section of the lipid raft, so that those proteins stay in place. And so, this lipid raft has a particular function that the rest of the membrane; that this part of the membrane here, and this one here doesn't have. And so, there can be different lipid rafts on different sides of the membrane. So, what we talked about is the lipid bilayer, its composition. It's made up of different types of lipids that have different characteristics, whether they're short, long, saturated, unsaturated, different types of lipids including cholesterol, and we've talked about the fact that the two different sides of the membrane don't look the same. They're different. They have different lipids. They have different proteins. They can have different enzymes that affect the lipids on either side, and they have different lipid rafts. And so, this creates this bilayer that's not only just acting as a barrier, but has all these different domains that are unique to that particular portion of the membrane, and that's going to be super important when we start talking about signaling networks and interacting with other cells. So, the bilayer is really that asymmetrical part of the bilayer is super important for allowing different things to happen on either side of the membrane. So super crucial for cell biology. So, with that, let's move on.

Lipid Assembly

Okay, so now let's talk about lipid assembly. Lipids have to be synthesized somewhere and then travel to the places in the cell they are needed. Remember, numerous organelles are encased in lipids, including the Golgi apparatus that contains numerous lipids. The plasma membrane and different vesicles in the cell also contain lipids. Lipids are assembled in the ER. Lipid synthesis occurs only on a particular portion of the ER, specifically on the cytosolic surface. This means that lipid synthesis happens where the ER interfaces with the cytosol. There, lipid synthesis constructs one monolayer; it just creates one lipid on the side of the cytosolic face of the ER. Subsequently, enzymes called scramblases intervene to form the bilayers. Scramblases transfer a lipid from the newly formed monolayer and scramble it to the opposite side. Sometimes, I receive questions about flippases and whether they are similar to scramblases. Although their functions are somewhat similar, they are two distinct proteins. Flippases specifically target certain lipids and flip them to the opposite side to maintain an asymmetrical membrane, whereas scramblases are not specific. They are involved in the random mixing of lipids to form a bilayer and do not target specific lipids.

Once these new membranes are formed on the ER, they pinch off and form small vesicles. These vesicles then travel to their required destinations, such as the plasma membrane or the Golgi apparatus. Some lipids remain in the ER, as it also needs lipids, but most are transported to other organelles.

Now, let's discuss a term that you will find in your textbook: "lipid droplets." These are essentially vesicles filled with excess lipids, serving as a storage solution for lipids synthesized by the ER but not immediately needed elsewhere. Much like how, in humans, excess fats are stored as fat in fat cells, cells store excess lipids in lipid droplets. Notably, adipocytes (fat cells) contain numerous lipid droplets.

Here we have the lipid bilayer synthesis process outlined. We have the ER, and a considerable number of lipids are being synthesized on one side of the membrane. Scramblases then come in and flip some of these lipids over to the other side, leading to a more evenly distributed lipid bilayer. Once this process is completed, the resulting structure pinches off from the ER and travels to its new location to augment the lipids in another organelle. That's essentially how lipid assembly works. With that explanation, let's move on.

Which of the following is not a form of lipid movement in the bilayer?

• A. Traverse diffusion
• B. Lateral diffusion
• C. Flippase diffusion
• D. Rotational diffusion

Of the following lipids, which of the following is most rigid?

• A. Phospholipids
• B. Sphingolipids
• C. Glycolipids
• D. Steriods

Of the following movements a lipid can do in a membrane, which is the most rare?

• A. Traverse diffusion
• B. Lateral diffusion
• C. Flippase diffusion
• D. Rotational diffusion

When the cytosolic face of a vesicle membrane fuses with the cytosolic face of the plasma membrane, all of the lipids found in the cytosolic face remain facing the cytoplasm.

• A. True
• B. False

In which cellular compartment are lipids synthesized?

• A. Nucleus
• B. Endoplasmic Reticulum
• C. Golgi
• D. Vesicles

Which of the following molecules is able to increase the rigidity and decrease the flexibility of a membrane?

• A. Phospholipids
• B. Cholesterol
• C. Proteins
• D. Glycolipids

Here’s what students ask on this topic:

What is the lipid bilayer and why is it important for cells?

The lipid bilayer is a fundamental component of cell membranes, consisting of two layers of amphipathic molecules like phospholipids, sphingolipids, and glycolipids. These molecules have hydrophobic (water-repelling) tails and hydrophilic (water-attracting) heads, creating a hydrophobic core and hydrophilic surfaces. This structure is crucial for maintaining the integrity of cells, allowing selective permeability for the intake and expulsion of materials, and protecting the cell from external environments. The lipid bilayer's fluidity and self-sealing properties are essential for cell survival, enabling dynamic interactions and adaptability to various conditions.

How does cholesterol affect the fluidity of the lipid bilayer?

Cholesterol plays a significant role in modulating the fluidity of the lipid bilayer. It is a rigid molecule that inserts itself between the phospholipids in the membrane. At high temperatures, cholesterol helps to stabilize the membrane by preventing it from becoming too fluid. Conversely, at low temperatures, it prevents the membrane from becoming too rigid by disrupting the regular packing of phospholipid tails. This dual role ensures that the membrane maintains an optimal fluidity, which is crucial for proper cell function and membrane integrity.

What are the different types of lipids found in the lipid bilayer?

The lipid bilayer is composed of various types of lipids, each contributing to its unique properties. The primary types include:

• Phospholipids: The most abundant lipids, with hydrophilic heads and hydrophobic tails, forming the basic structure of the bilayer.
• Sphingolipids: Contain a sphingosine backbone and are involved in protecting the cell and maintaining membrane stability.
• Glycolipids: Lipids attached to carbohydrate groups, playing a role in cell recognition and signaling.
• Sterols: Such as cholesterol, which modulate membrane fluidity and stability.

What is the fluid mosaic model of the lipid bilayer?

The fluid mosaic model describes the structure of cell membranes, highlighting their dynamic and flexible nature. According to this model, the lipid bilayer is not a static structure but a fluid one where lipids and proteins move laterally within the layer. The 'mosaic' aspect refers to the diverse array of proteins, lipids, and carbohydrates that are embedded in or attached to the bilayer, each contributing to the membrane's functionality. This model emphasizes the membrane's ability to self-heal, adapt to changes, and facilitate various cellular processes.

How do scramblases and flipases contribute to the asymmetry of the lipid bilayer?

Scramblases and flipases are enzymes that play crucial roles in maintaining the asymmetry of the lipid bilayer. Scramblases randomly move lipids between the two layers of the bilayer, ensuring an even distribution during membrane synthesis. In contrast, flipases are specific enzymes that selectively transfer certain lipids from one side of the bilayer to the other, creating and maintaining the asymmetrical distribution of lipids. This asymmetry is vital for various cellular functions, including membrane curvature, signaling, and interaction with the extracellular environment.