The Science of Everything Podcast - Episode 116: The Cell Membrane

Episode Date: March 30, 2021

An introduction to the cell membrane, including a discussion of the structure of the bilipid membrane, an overview of the structure and function of membrane proteins, a review of the fluid mosaic model, and a discussion of mechanisms of membrane transport, including both passive and active transport. Recommended pre-listening is Episode 10: The Cell, and Episode 18: Biochemistry Basics. If you enjoyed the podcast please consider supporting the show by making a PayPal donation or becoming a Patreon supporter. https://www.patreon.com/jamesfodor https://www.paypal.me/ScienceofEverything

You're listening to The Science of Everything podcast, episode 116, the cell membrane. I'm your host, James Fodor. So in this episode, we're going to pick up from where we left off way back in episode 10 when we talked about the cell. Well, I mean, I've talked about other aspects of the cell since then, but in particular, in the cell we talked, I gave an overview of the different components of the cell and the organelles and how they work together. And one of the things that I didn't discuss in detail was the cell membrane. And so in this episode, I'm going to rectify that, and we're going to talk about the cell membrane, which is basically the wrapper that holds in all of the other organelles and components of the cell. And specifically, I'm going to look at the bi-lippid membrane layer that forms the membrane

and discuss its components and structure. Then I'm going to talk about membrane proteins and some of their structures and functions, and we'll conclude by talking a bit about membrane transport, including active and passive transport and some of the mechanisms of that. So recommended pre-listing, as you might have guessed, will be episode 10, the cell, and also episode 18, bichemistry basics will probably be helpful because I'll be talking about proteins and lipids a lot, so a bit of background will be useful there. So without further ado, let's jump in and start by talking about the bilipid membrane layer, or the bilipid layer. So the cell membrane consists of a bilipid layer, which is a thin, fatty layer that separates the interior over the cell from the outside environment, which is called the extracellular space. So there's the intracellular space, which is where you have the cytosol and the organelles and nucleus and all that.

And then there's the extracellular space, which is just outside between all of the cells, which is the outside environment. And so there needs to be a separation so that the cell can maintain its integrity and conduct the biochemical. reactions that it needs to in order to function and separate that out from everything that's happening outside. So obviously something needs to do that and the cell membrane is what takes the job. Although I should say the cell membrane is what does the job, but that's only true for organisms that don't have a cell wall, like plants and fungi have cell walls, and sometimes the bacteria also have cell walls. So in that case, there's more complexity as to the sort of barrier between the intra and extra cellular environments. But here I'm primarily going to

to be talking about animal cells, which don't have cell walls, and so therefore the cell membrane is what does the job there. So I mentioned that the cell membrane consists of a lipid bilayer, so biolay just means two, so there are two layers there, and lipids, you may recall from biochemistry basics or elsewhere, are hydrophobic molecules, so they are, like, oil and fats that exclude water, and they make up the two layers of the lipid membrane. Now, there's a very good reason as to why the cell membrane consists of lipids, and it's because one of its main purposes is to exclude the various charged ions, or ion is charged by definition, that exist in the solution, both inside the cell and outside the cell. It needs to be able to prevent those from just

moving around wherever they like, because that would disrupt a lot of the intracellular biochemical functions. And as we'll talk a bit about later, non-polar lipid compounds are very good at doing that. So that's one of the reasons why the cell membrane consists of a lipid bilayer. So there's this double layer of lipids surrounding the cell, and there's various proteins that are sort of studded in that membrane, which perform various functions that we'll get into later. So that's the basic picture of what the cell membrane is. It's a double layer of basically like thin fatty substance with these membrane proteins studded throughout. The cell membrane is very important because apart from just sort of keeping the cell sealed

off from its environment, it also controls the movement of substances into and out of cells, and therefore the organelles from the cells. So if ever a cell needs to produce products that it needs to release into the extracellular space, it has to do so through the cell membrane. The cell membrane also will mediate the intake of nutrients, such as, you know, sugar or other ions or minerals into the cell that it may need for metabolic function. Furthermore, the cell membrane is also responsible for most of the intercellular signaling processes that are essential for multicellular organisms, and even some unicellular organisms, but especially multicellular organisms. So things like cell adhesion to other cells or to other parts of the tissue and the organs

that they're part of, ion conductivity, cell signaling, signaling to the immune system, and for attaching to extracellular surfaces like the cell wall. So the cell membrane is not just a sort of a passive liner that the cell cell is inside. It was sort of thought that that was the case, you know, a few centuries ago when it was discovered. But these days the cell membrane is one of the most important, is understood to be one of the most important structures or organelles of the cell, because it's responsible for all of the transport and all of the signaling parts of it. So, let's look a bit more into the structure of the cell membrane. The cell membrane is made mostly out of phospholipids. So I mentioned that it's a

lipid bilayer. Well, now I'm talking about specifically the nature of these lipids, and they're called phospholipids. They're so-called because they consist of a head and a tail, and the tail are hydrophobic tails, so there's two of these, so it's like it's got two legs, kind of, and these are hydrophobic, so they're long, mostly saturated carbon-to-hydrogen chains, although there's often some unsaturated bonds in there, which give some kinks to the tail. Those are the, that's the hydrophobic part, that's what makes it a lipid, but in addition, there's the hydrophilic head, and this hydrophilic head is made up of a glycerol molecule bound to a phosphate. group. So it's sort of phosphate, glycerol, and then the two fatty acid chains.

Overall, this makes up the phospholipid. He's got the phospho-lippid and the lipid bit. So these are, well, they are lipids, but they are actually amphipathic lipids. What this means is that there is a hydrophilic bit and a hydrophobic bit. So it's sort of like jewel. There's a bit that loves water and there's a bit that hates water. And this is very important because what happens actually is because of the amphipathic nature of the of the phospholipids. They structure themselves naturally, if you just sort of dump them in solution, they naturally gather themselves together, such that all of the tails, the hydrophobic tails,

the fatty acids, they point in the same direction and cluster together. And then all of the hydrophilic heads point in the other direction and cluster sort of together. And it turns out that they naturally organize themselves into these phospholipid bilayers. The reason for that is because if you sort of think about it, a phospholipid bilay, which is arranged in more or less a sphere, is able to have the outside layer with all of the heads, you know, like the hydrophilic heads of the phosphory lipids pointing outwards, and then the second layer has, inside the sphere,

has all of the hydrophilic heads pointing inwards. So on both exterior surfaces outside and inside, you've got the hydrophilic bits, the heads, pointing towards the water in solution. And then between those two layers, you've got the legs that point into each other, forming the lipid bilayer proper. And those regions pack together because, of course, they don't like water. These are the hydrophobic regions. But in packing together away from the water and protected from the water by the hydrophilic head,

they're able to achieve the favorable energy state. So basically, the cool thing about these phospholipids is that they spontaneously organized into actually single and also two-layer structures when you just put them in solution, because that is a favorable energetic state because the hydrophilic bits go near the water and the hydrophobic bits go away from the water and exclude the water. So they just sort of naturally form these membrane structures

by themselves spontaneously, which is pretty awesome. And so the cell membrane naturally sort of tends to maintain that structure. If you sort of peel a bit out or snip a bit out, it will naturally sort of refold back and smooth itself out because the lowest energy state is basically a spherical shape because otherwise you've got more of the membrane exposed to the solution that is that is favorable. So they tend to form these loosely spherical shapes.

And they are self-repairing as well. So if you cut them, they'll naturally sort of fold back and smooth over. So for a lot of these reasons, it's a very suitable substance for a cell membrane. Now, the cell membrane is not only made up of phospholipids. That's kind of like the basic building block, if you like. And there's not just one phospholipid molecule. There's many different subtypes, which I won't get into here, because it's a bit more advanced than we need to that are slightly different from each other,

and different types of cells and different types of organisms have slightly different composition. So it's not all uniform. There is variation. But in addition to these phospholipids, there are also proteins that I mentioned before that are studded throughout the membrane. So they comprise about 50% by volume of the membrane, which is actually quite a lot. So it's not really the case that it's sort of mostly phospholipids and then a few membrane proteins here and there. It's actually sort of half and half, at least at least. least by volume. I don't know how that works by weight. So there are lots and lots of proteins throughout the surface of the membrane. In addition to that, there are also cholesterol molecules.

So cholesterol is another type of lipid molecule, so it's also hydrophobic. And so naturally, it likes to sit inside the tail part of the membrane. So remember, you've got your bilipid membrane, you've got the hydrophilic heads on either side facing the extracellular space and the intracellular space. The side is on the other side. And between them, you've got the two layers of the fatty acid tails, which point in towards each other. And that region is hydrophobic region. So the cholesterols like to sit in there between the tails. They sort of squeeze in between the tails.

And cholesterol is a bit smaller than the phosphory lipids, so it can sort of sit inside there. and it's a structure that has these four carbon rings fused together, three rings with six carbons in it, then one with five carbons, and there's a little tail on it. Just look it up on Google Images or something, if you're interested in terms of what it looks like, but it doesn't matter too much for our purposes. Just know that it's a very different type of molecule to phosphory lipids,

except that it's also hydrophobic, and therefore it likes to sort of squeeze in between the hydrophobic tails in the phosphory lipids. and the advantage of having those cholesterol sort of studded throughout the, or squeezed in throughout the membrane, is that in regions that are high in cholesterol, they tend to be more rigid because basically it forces the phosphory lipids to pack in a bit more tightly and reduce the permeability between them. So it reduces the permeability of the membrane. We'll talk a bit more about that later and also helps it be a bit more rigid. And this is useful for things like lipid rafts, which we'll talk a bit about later and for other sort of structural functions of. of the membrane to have certain regions that are higher in the cholesterol concentration. Okay, so these are the main components of the bilepin membrane.

You've got the basic substrate, which is a phosphorylipers, then you've got the cholesterol studded in here and there in particular regions to give it extra sort of structure and rigidity and reduce the permeability, and then you've got lots of proteins throughout the entirety of the membrane, which perform lots of different functions. Now, it's important to understand that the lipid bilayer is a fluid, which means it's not rigid and sort of fixed in place. All of the different molecules are constantly moving around.

And this is largely because the forces that keep it together are relatively weak. They're strong enough to keep it together, but not strong enough to keep it rigidly stuck in place, like a crystal lattice or something like that. So the lipids and the proteins are all moving around relative to each other and are sort of a sea. You can sort of imagine the proteins are kind of like boys that sort of bob in the sea and move around, although they're very densely, it's a very dense population of these boys. It's not just a few of them. That gives you some idea of what's happening here. It's a very complex ecosystem. The degree of fluidity varies depending on the exact structure of the membrane, so that depends on things like the nature of the phospholipid molecules, like the type of them, the number of cholesterol's, temperature, and other things like that.

The number of saturated hydrocarbon tails in the fatty acid tails of the phospholipids also matter. So the more double bonds there are, the more kinks there are in their tails, which means that they can't pack in as closely. So saturated hydrocarbon tails with no double bond unsaturated kinks result in the least fluidic regions or least fluidic membranes. And I mentioned also cholesterol stiffens the membranes too. So this is called the fluid mosaic model of the membrane. It's basically the proteins floating about and moving relative to each other in this sea of the phosphorylipy. with the studded cholesterol throughout it. That's the basic model that's been around for about 50 years now of the cell membrane,

and it's still widely taught and used. However, it is important to understand that it's not complete. There are things that this fluid mosaic model leaves out. In particular, I'll focus on a few here. So one is a phenomenon called lipid rafts, which I think have been appreciated only fairly recently the last few decades. So these lipid rafts, which I just mentioned earlier, are little platforms in the membrane.

They're quite small. We're talking on the order of nanometers, or maybe a few tens to hundreds of nanometers. And basically, they consist of a small region with maybe a couple of proteins, maybe a few hundred phospholipids or something, which diffused together, diffused laterally together, like across the membrane.

And they're basically, they're like a little raft in the sea. They sort of move as a unit throughout it. And they generally sort of maintain their integrity through a higher concentration of a particular type of molecule called sphignolipids as well as cholesterol, which help to give it a bit more structure and integrity. And they tend to bulge out a little bit relative to the surrounding membranes. You can see some interesting visualizations of this where it shows like that they're kind of bulged out either side of their membrane and move around relative to each other.

So this is a way of keeping protein complexes together. Maybe there's a bunch of membrane proteins that the cell needs to be in close proximity to each other to serve a particular function. So they'll be located in one of these lipid rafts. And I think that there's probably other functions as well that aren't fully understood. But this is an ongoing area of research about exactly how these rafts operate. So that's one sort of addition to the original fluid Mosaic model. Another addition or additional aspect here is the importance of the cytoskeleton.

So I would have mentioned this briefly in episode 10, but I will at some point do a whole episode on this, the cytoskeleton is very interesting and a very complex structure. But it's basically a series of tubules, a system of tubes, that keeps the cells structured and hold it together. But it does much more than that as well, because it moves things around and it directs cell division and it has a whole bunch of functions. But it's also known that the cytoskeleton helps to maintain the locations of proteins in

the membrane and helps to maintain particular regions of the membrane distinct from each other, and there's proteins that are embedded in the membrane that then connect to the cytoskeleton, and these can move around a particular way. So again, that's an ongoing area of research, the relationship between the cell membrane and the cytoskeleton. A third sort of addendum or extension of the fluid mosaic model is the fact that the plasma membrane is asymmetric. So it's not just that there's a fluid which has, you know, the outward direction and the inward direction, but the outer layers of the membrane are quite distinct from each other. structurally and functionally.

I mean, they're still basically the same, like, you know, phospholipids and proteins and cholesterol and so on. But the composition in terms of the types of phospholipids and the amount of cholesterol and the types of proteins are all quite different between the two layers. And that asymmetry is functionally very important, of course, because there's many types of proteins that you only want inside the cell and others that you only want outside the cell,

you don't want them getting mixed up. Also, the difference here helps the cell to distinguish, excuse me, the difference here helps the organism to distinguish between the outside of a cell and the inside of a cell. And that's important if the cell dies, right, and exposes its inner membrane to the extracellular matrix. Because then when the various immune cells and other things come along, they can detect the difference between,

oh, this is not the membrane I expected to see. This is actually the inner membrane. And that shouldn't be here. I shouldn't be able to see that because it should be inside the cell. So that means something's gone wrong, that the cell's dead generally. And often that's because they may be because of infection or tissue damage or something. So that asymmetry plays a lot of important functions.

So before we move on to talk about membrane proteins, I just wanted to mention one other important aspect of the, I guess the fluid mosaic model, and that is relating to the asymmetry of the two different, the inner and out of membrane. And that is that although there is great lateral movement of the lipids and the proteins, the movement between the inner and outer layers is quite restricted.

So proteins generally only exist in one layer or the other. I mean, there are some proteins, of course, they extend over both layers. But if there's a protein that's only in one layer, then it will stay in that layer. It won't go to the other one for the most part. Also, phospholipids will usually stay within one within either the inner or the outer layer. They can flip between the two, but that's quite rare. So mostly they'll stay around within one layer. There are particular enzymes that can help phospholipids to flip between one side of the membrane

and the other side. And these special proteins are called flipases and flop aces. So flipases are the ones that move lipids from the outside to the inside surfaces of the cell, whereas the flop aces move from the inside to the outside of the cell. In addition, there are so-called scrambleaces, which can move in either direction, and they scramble the orientation. So these are important for ensuring that particular lipids end up on a particular side of the membrane, and for building things like lipid rafts or other structures. So, that completes a discussion of the basic structure of the bilipid membrane and the fluid mosaic model. Let's now move on to talk about membrane proteins.

So we know, as I mentioned before, that about half of the membrane biolium, it consists of proteins that are studded in the bilipid membrane structure. So what do all these proteins do and how are they attached to the membrane exactly? well, the proteins carry out a very wide range of functions associated, particularly with membrane transport and signaling. So these are two of the major functions of the membrane, aside from just maintaining the intracellular environment, and they're basically carried out by proteins. So when you need to get something from one side of the memory or the other, you're going to have a protein helping you, or multiple proteins. Also, when the cell needs to signal to other cells in the organism or receive information about its external environment, that's done through proteins. So these are the main function of membrane-bound proteins.

There are other membrane-bound proteins that just sort of use the membrane as a sort of a convenient anchor point. So an example of this, although it's not on the cell membrane, would be the various proteins involved in photosynthesis and also in oxidative phosphorylation in the production of energy in the mitochondria, because both of these processes utilize a number of proteins that are embedded in the membranes. And they're not embedded on the membrane of the cell itself, but of the organelles. either the chloroplast or the mitochondria. And I've talked about that in previous podcast episodes, so I'm not going to get into that here.

But the point there is that it's just convenient to use a membrane-bound structure because of the ability to use a gradient, a proton gradient across the membrane as basically a battery to store energy, which then you used to produce ATP. So there are other proteins that basically just stick in membranes as a sort of a convenient way to structure their activities and don't necessarily, you know, like photosynthesis isn't a transport or a signaling process per se, because. because it's all inside the cell. But here we're focusing mostly on the cell membrane itself

and the functions of proteins in that particular membrane, not membranes within the cell. When we're talking about the cell membrane, there are three main types of proteins in terms of the structure. There are integral proteins, peripheral proteins, and lipid-anched proteins. So integral proteins are ones that are directly stuck inside the plasma membrane. Now, they can either be stuck in one side of it,

either the outside part or the inside layer of the membrane, they can be a trans membrane protein, which means they extend across the in both layers of the membrane. So trans membrane proteins are especially important for transport, because of course you've got to get things across the whole double layer structure of the membrane, whereas single layer integral proteins may be probably more likely to be either signaling molecules to the outside of the cell or serving some sort of enzymatic role within the cell, in which case is probably going to be on the inside layer. And proteins like that don't necessarily need to extend across the entire membrane. So those are the integral proteins. Then there are the lipid anchored proteins.

So these proteins aren't directly inside the membrane. Instead, they're covalently bound to a lipid, which is then inside the membrane. So they're basically bound to a phospholipid of some sort. They're kind of just on the outside of the membrane, they are attached to it by being bound to a phospholipid of some kind. So they're more peripherally attached, but still directly attached to the membrane. and they also may be enzymes or signaling molecules or some sort. Not really going to be a transport protein if you're attached like that

because you really have to be able to transport something across the bilipid membrane for that to work. Then the final type are the peripheral proteins. And these are proteins that aren't even covalently attached to the lipid membrane. They're just sort of weakly associated with it, with vandywell forces or something like that. And it turns out there are actually large numbers of these peripheral proteins on either side of the membrane. I think there are more on the extracellular side, because it turns out that there's actually

lots of proteins and, well, lipids and carbohydrates and other stuff just circulating in the extra cellular matrix. And some of these just sort of attach onto the outside of the cell and become peripherally attached proteins. And some of them may form a function or some of them may just sort of happen to be there. So it becomes a little bit of a semantic point about, well, is this part of the cell that's a peripherally attached protein on the external surface, or is this sort of something that's in the extracellular environment that is just attached to the outside of the cell? Like, is it part of the cell or not? There's no real clear answer to that, because, I mean, you could look at it either way, really, which is kind of interesting, that cells are sort of very,

especially, I guess in multicellular organisms, they're very closely connected to the extracellular environment. You can't really understand the cell without thinking about the environment that it exists in. So, that's the sort of a structural. discussion of the different membrane proteins. Let's not talk about some of the different functions. I mentioned some of them already, but we'll just go through a few of them here. I'm not going to talk about them in any detail. I've talked about that in some previous episodes, such as when we did photosynthesis and when we did, we talked about mitochondria and its function, and more will be discussed later in future episodes. We talk about other functions of the membrane

proteins, but here I'm just going to talk about some of their generic functions. So I've already mentioned transporters. So these are proteins that permit a specific substance to enter or leave the cell. More on that in the next section where we talk about membrane transport. There are enzymes, so these help their cell to carry out different, you know, catalytic functions. These are going to be on the interior of the cell for the most part, attached to the inner surface. There are cell surface receptors, so they're going to detect chemical changes in the environment or messages from other cells. So these are going to be on the extracellular surface. There are identity markers. So these are basically proteins that give information about what type of cell it is.

and these are these basically exists so that the immune system knows what's going on and what type of cell exists there and marks it as a self-cell as opposed to some sort of imposter from the outside so these are obviously on the external surface and finally there are cell adhesion proteins so these are proteins that help form bonds to neighboring cells to help them join together so for example gap junctions proteins involved in forming gap junctions which are basically connections between adjacent cells are an example of that and so they're going to be i mean they may extend across the whole a lipid membrane all they may just be on the external surface. So those are some of the functions performed by these proteins, again, largely involved in transport and signaling and interaction of the cell with its environment, although there are some that are just enzymes that happen to be in the cell membrane. Cell membrane proteins can come in many different forms. Some of the structures that are quite common are alpha helices

that extend across the entire bilipid membrane structure, so that the helix has to be a certain length. I forget the number of amino acids, like 20 or 30 or something, to extend across a typical bilipid layer. And there are many of these proteins that actually extend multiple times across the membrane. So it's sort of like a snake that there's a helix that extends across the membrane once,

and then there's a, and then the protein kind of turns around, and then there's another helix that goes back, and then it goes back and forward, back and forward. There are many different types of proteins that have this structure, and it obviously forms a very tight bond with the membrane, so, you know, it's not coming out of there or anything like that. And we'll talk more about that, I think, when we get to the episode where we talk about cell signaling, because there are many of these signaling and receptor molecules that have this structure.

Another type of structure that you will see with integral proteins in the membrane is a beta barrel. So if you recall biochemistry basics when we talked about protein structure and function, and alpha helix, well, it's kind of like a helix that curls around. This is good for extending across the bilipid membrane because you can have the hydrophobic, regions of the protein on the outside and the hydrophilic regions on the inside protected from the hydrophobic parts of the membrane by being enclosed inside. A different way to achieve that is to have a beta barrel. So beta sheets are a different secondary structure of proteins where it's these sort of sheets that are usually anti-parallel to each other. And a beta barrel is like a bunch of these sheets

that have been curled around. So imagine a piece of paper and you curl it up on itself and it forms a funnel. That's basically what a beta barrel is like. It's this funnel that forms a hole through the membrane. And there can be quite a large hole as far as these things go. So these are particularly used for transport, it's to transport things from one side of the membrane to the other, because the beta sheet wrapped around itself can form a hole through the membrane, which things can be transported across. One thing that I wanted to mention also about membrane proteins before we finish this subjection is that the plasma membrane, the external surface of the plasma membrane in at least eukaryotic cells, is covered in carbohydrates. It's pretty much

like a lawn of carbohydrates. And some of these are directly embedded into the plasma membrane, while others are attached to the membrane proteins and things called proteoglycans. The purpose of this kind of lawn of carbohydrates, which again covers basically the whole membrane and the surface proteins, is to provide protection to the cell

and reduce unwanted protein-protein interactions with its environment. So if you're thinking about a cell membrane as just kind of a bag that covers the cell, then you need to think again, because not only is it a dynamic lipid membrane with all of these different proteins studded through it. But also there's an entire lawn of covering carbohydrates that covers the external surface.

And remember that there's these lipid rafts that have particular structures that are moving across it and there's the cytoskeleton interacting with it, pulling bits hither and there. And then there's interaction with external singling and other cells in the environment. So there's lots of complex stuff going on here. It's a very dynamic interactive structure,

and it's not just a sort of a passive bag. All right, the last part of this episode, we will talk about transport across the membrane, which is one of the important functions of the plasma membrane. Before we get into that, we'll talk, well, as an introduction to that, let's talk about diffusion because pretty much all of this is dependent on understanding diffusion. And I would have talked about this in the previous episode, but we'll just go over it here again. So diffusion is the process of some solute, so basically anything dissolved in water, moving down its concentration gradient through random motion.

So just spontaneously, anything in a solution with the concentration gradient will move down its concentration gradient. So it will move from where it has higher to where it has lower concentration. And this is just simple mathematics, right? Because if you've got, you know, on one side of the room, there's 10 basketballs that are bouncing around. In the other side, there's one. There's 10 ways that the basketballs can go from being on the basketball rich side to the

basketball poor side, right? But there's only one way that it can go to the other, where it can go from the basketball poor side to the rich side, right? So just by chance, you're going to have many more basketballs going from the 10 side to the one side than vice versa. So you're going to end up with more, on average, more basketballs moving to the emptier side. And that's basically what's happening here as well. There's just more ways for a solute to move into a solute poor region than it is for solute in the poor region to move to the rich region. So that tends to happen over time. So it occurs spontaneously. The way we say that is that solutes move down their concentration

gradients. If you want to push a solute against its concentration gradient to increase the gradient rather than diminishing it, then that requires energy to do. And the cell has mechanisms for doing that, which we'll talk about in a little bit. So the bilipid membrane inhibits, but it doesn't completely prevent, but it significantly inhibits diffusion for a lot of substances by acting as a barrier. So it sort of prevents diffusion from happening, at least to a large extent. However, some substances are still able to cross the membrane more readily than others. It depends on the nature of the substance. So I mentioned this before, in particular ions, so things like protons, sodium ions, potassium ions, chloride ions, magnesium and so forth, they basically cannot cross the lipid membrane at all, or to a very small extent.

And the reason is because they are charged and they are therefore basically excluded from the hydrophobic inner core part of the biolipid membrane. There's just no way they're. can get through there because they're going to be excluded. When something is hydrophobic, it also excludes anything that's charged because water is a polar molecule, you recall, so it's the polarity that is really excluded, and anything that's charged is sort of highly polar in that sense. I mean, it's not literally a polar molecule if it's just one charge, but the point is it's still going to be excluded from a hydrophobic region. So those ions, those small ions are not getting across the plasma membrane without help. Now, there are ways to get across, but they're not going to

diffuse across. At the other extreme, hydrophobic molecules, which again is like the lipid, the fatty acid parts of the lipid membrane itself, that's hydrophobic. So hydrophobic molecules are going to get through it quite easily because they can just glide right through because they're not excluded by the hydrophobic fatty acid tails of the phosphory lipids in the membrane. They're just at home there. So they can go on right through and diffuse across the membrane. Hydrophobic molecules like benzene can quite easily get in, as well as gases. So oxygen, carbon dioxide, nitrogen, they can all get in. So that's very, very, important of course because cells need a supply of oxygen so that can just diffuse right across the membrane. Now when we're talking about uncharged molecules

that are polar so we know that non-polar molecules can get in that those are the hydrophobic ones and charged ions can't get in. What about uncharged so not ionic but polar molecules? Well if they're small they can get through although not all of them so the rate of diffusion is diminished but not completely eliminate. So things like water can cross the plasma. membrane, but the rate at which they can cross is slower because they're going to have some trouble getting through the hydrophobic region, obviously, but they can eventually leak through. Whereas large uncharged polymolecules, like glucose, for example, basically can't get through

that. They can maybe cross a little bit, not quite as excluded as the small ions, but they're going to have a lot of trouble getting through. So basically gases are, and hydrophobic molecules are the things that can most easily cross the plasma membrane. Other things like water, glucose, and ions either can't get through very well or can't get through at all. So they're going to need help to get across. And that help occurs through proteins, of course, transport proteins. So there's two main types of transport proteins that exist in the plasma membrane. Carriers and channels. The difference between the two, they do the same thing. They allow things to get across the plasma membrane. But there's an important difference between them. So a carrier is something that cannot be open

spontaneously to both the outside and the inside. So it's basically a directional protein. What it does is that it will be open on one side. It will bind to something and then it will change its confirmation and then let that thing go on the other side. So it has to sort of flip around. It's like a door that can only be open one way, which I guess most doors aren't like that. But if you can imagine, that's kind of how it works. Whereas a channel is just like a hole in the protein. I mean, it's not literally a hole. There's more. structured to it than that, but it is open at both ends at the same time. And because of that, channels allow much more rapid, like hundreds of times more rapid, or even thousands of times more

rapid movement of solutes or whatever it is that is crossing the membrane, much more rapid transmission of the solutes across the membrane in channels compared to carriers, because the carriers can only do it sort of one at a time or a few at a time, if you like. They have to face one way, they bind whatever they're moving like glucose or whatever, then they change confirmation and they let it out at the other end and then they have to change confirmation again when the when the solidate dissociates and then they go back so it's a lot slower than if you just let things through like in a funnel sort of thing so that's the difference between carriers and channels now carriers and channels can both work as passive or active

transporters so passive transport is just what happens when it's something's when a solute is moving down its concentration grading when it's moving from highly concentrated to low lower concentration. That will just happen naturally. That's why it's passive. You sort of don't have to do anything. There has to be a way it gets across the membrane, so it will need some sort of transporter, be it a carrier or a channel, doesn't matter either way. But as long as it's got that, it will just move spontaneously. It doesn't need energy to do that. So it's important to understand there's a difference between whether something's active or passive. That tells you whether it needs energy or not, for it to happen, and whether a solute is able to move across the plasma membrane by

itself or requires the help of a carrier or a channel. Most substances do need the help of a carrier or a channel unless they're hydrophobic molecules or gases. Most other things will need some sort of protein to get them across. But it's a second question as to whether it needs energy added to that. Because if it's moving down its concentration gradient, then it won't need energy, even if it still needs the help of a protein to get across. It doesn't need any extra energy to do that if it's moving down its concentration gradient. But if it's moving up its concentration gradient will need energy. And that is called active transport. So active transport is just when you're moving something against its concentration gradient. You're increasing the concentration on one side

even further than it already is. And so you need energy to do that. There's three basic sources of energy that the cell can use to do this. And they are ATP, which you may recall is the like the energy currency of a cell, adenosine triphosphate. So there's like three phosphate groups stuck on the end of an adenosine, which is like a modified nucleotide. And the triple phosphate groups basically like a spring. They have very highly energetic bonds, so you can use that as an energy source. The two other energy sources that the cell can use to power active transport are light and an ion gradient. So you're familiar with an ion gradient if you've listened to the episodes on photosynthesis or on glycolysis and oxidative phosphorylation because those utilize an ion

gradient across a membrane, a proton gradient in those cases. And an ion gradient is essentially just using the concentration gradient of one ion to power another concentration gradient. So let's go through those a bit more details. Let's start with ATP. So transportors or enzymes that use ATP to power active transport are called ATP aces. A little bit hard to say, but they require phosphorylation of the protein and binding of some sort of whatever substance is going to be transported to induce a conformational change, which then drives the solute against their concentration gradient. So then after the conformatical change has occurred, it will basically spit out the

whatever it's carrying, the solid that is carrying on the other side of the membrane, triggering another confirmation change, which moves it back to its original confirmation, and then the process can continue. But in order for that to happen, it needs continual addition of ATP molecules because this costs energy to do that. Many of these can actually operate in passive or active mode. So it's not so much, like, which way they're moving things. It's just natural.

They'll move things down the concentration gradient. If you want to move them the other way, then you're going to need to power them. So that's ATP. Light is a source of active transport in some systems, and probably the most well-known would be photosynthesis. And so I've already talked about that. Photosynthesis uses light to power the production of a proton gradient across the thylacoid membrane inside chloroplasts in plants.

So we've done an episode on that, and you can look into that if you want to know more details about how that works. And the final source of energy that I mentioned is the ion gradient. So this occurs in a particular type of carrier called coupled carriers. So these are carriers that they don't just carry one thing at a time. They actually carry two things. Basically, there'll be the thing that you actually want to transport, and then the other thing that you're using to power it.

So it's sort of like carrying a passenger to work, except somehow the passenger powers your car at the same time. I'm not exactly sure what a good analogy would be there. Maybe like a tandem bicycle where you have another person, riding with you and they help to power you as your ride so you don't have to ride as hard. I don't know if that actually works that way because I've not ridden a tandem bicycle before, but hopefully you get the idea. The idea is that instead of just transporting one thing against its concentration gradient,

which takes energy, you can actually transport another thing at the same time, generally an ion, down its concentration gradient, which releases energy and provides a source of energy for the other thing to go against its concentration gradient. So it's like a two for one, and the upside is that you don't have to use 80s, to power the active transport. The downside is that you do need a source of some sort of ion gradient that you're going to then deplete. You're going to move things down across that concentration gradient in order to transport

whatever you're trying to move. So you will need a way of replenishing that concentration gradient. So you'll need something else that is then pumping those ions back out. So an example would be if you've got protons outside the cell, they can be used to transport some sort of product like glucose outside of the cell. but in so doing you're going to deplete the proton gradient that you used to do that, so you're going to need to pump protons back outside of the cell in order for that to be sustainable. This is quite a common technique that's used in cells.

So there's two ways you can do this. You can move the ion in the same direction as the other product that you're moving, and that's called enzymes that do that are called Simporters, because they're moving both things in the same direction. Or you can move them in the opposite direction, those are anti-porters. It's basically the same thing. It's like which direction do you happen to have an available, ion gradient in. If it's in the same direction, then it'll be a simporter, opposite direction,

it's an antiporter. But otherwise, it's the same basic principle of using one gradient to power, passive diffusion, to power an active transport against a concentration gradient of something else. Now, one very important example of transporting ions across the membrane is the sodium potassium pump. And this is a very critical enzymatic system here, which consumes about one third of all the energy used by an average cell that's not currently dividing. So if cells are not dividing, then about one third of their energy is going to just the sodium potassium pump. So it's very, very important. The reason why it needs so much energy and needs to be active all the time is because most animal cells must maintain a higher internal concentration of potassium ions and a lower

concentration of sodium ions compared to the extracellular fluid. And the purpose of that is essentially to control the osmotic pressure across the membrane. Basically because you think about the intracellular environment of the cell, there's lots and lots of stuff there. There's DNA, there's proteins, there's compartments, you know, organelles, lots and lots of stuff going on there. And most of that stuff doesn't exist outside of, just in the extracellium matrix. There's some stuff there, but there's not nearly as much stuff as is contained in the side of the cell. That results in a relatively water deficient environment. So what tends to happen is when you have a high concentration of some solute, which here includes all the proteins and other stuff inside the cell,

is that water is going to tend to come in. And it's the same thing. It's diffusing across this concentration gradient, right? You've got all this highly concentrated proteins and other stuff inside the cell, and relatively have low concentration of that. The other side is going to want to come in across this concentration gradient. If that was allowed to happen without being controlled, then the cell would basically build up osmotic pressure across the membrane and eventually burst.

And this does happen in cells if you deactivate the sodium potassium pump. So the cell will die if it's not able to control, the osmotic pressure in this way. And the Cernium potassium pump is able to do that by basically pumping ions out of the cell. So ions are very good for controlling osmotic pressure because there's lots of them. And it's the number of molecules that's really important for osmosis here, not necessarily their size. So if you can pump lots of ions outside the cell, you can sort of offset a lot of the proteins and other stuff that's inside and maintain an osmotic balance. So that's what the sodium potassium pump is doing it. Basically, it's pumping ions outside of the cell, on net.

But it's a little more complicated in that. It doesn't just pump ions out willy-nilly. It exports three sodium ions for every two potassium ions that it brings in. So it brings in potassiums and exports sodiums, but it exports more sodiums than it brings in. So on net, it exports a single positive charge. And so that has effects on the charge of the cell. So on balance, there'll be a negative resting cell potential, and that's used for neurons. Check out the episodes I did on that if you want more detail about how that works. But in addition, there's also, it also helps reduce the osmotic pressure by reducing the number of ions floating around inside the cell. And that helps to control the osmotic pressure.

So this is absolutely essential for all cells, especially important in neurons, because they're actually using that potential to transmit information. The mechanism by which the sodium potassium pump works is sort of complicated. So there's a few stages here. Basically, this is an ATP ace. so it requires ATP in order to work. That's why it's using so much of the energy of the cell. And it works as a carrier. So it's not a channel.

So it's one of those things that is directional. So basically it collects up three sodiums from inside the cell. That triggers a conformational change, which kind of directs the protein to the other side, the extracellular side. It then releases those sodiums and collects two potassiums, which then triggers another conformational change, which brings it back the other way and releases those potassium.

But it needs an ATP to be able to, keep doing that because it does take energy to pump the sodium against its concentration gradient. So this is an example of a particularly important protein carrier, which is active, which is highly active in essentially all cells. So that concludes the discussion of membrane transport and, as such, the discussion of the cell membrane. So just as a quick recap, we talked about the structure of the biopid membrane and the fluid mosaic model, some of the limitations of that. We talked about membrane proteins and some of the functions that they carry out. the different structure and types of those.

And we also talked about membrane transport and difference between carriers and channels and the need to maintain osmotic pressure and the various sources of energy that can be used to power active transport. So hopefully you found this episode interesting. In the next couple of episodes, we're going to look at some other aspects of membranes. So we're going to look at intra-cellular membranes and the compartments that exist inside the membrane and how those are used for sorting. And we'll also look more about cell signaling and how receptors on the cell are able to receive and transmit signals between different things. sells. So look forward to those. I'll be coming up in the near future. If you enjoy the show, then please consider supporting us by going onto iTunes or whatever aggregator you use and giving us a favorable review. That really does help to spread the word about the show. You can also,

if you'd like to be particularly generous, make a financial contribution, which helps me to devote more time to the show. You can do that via PayPal or by becoming a Patreon supporter. The links to that should be in the show description. Also, feel free to send me an email. My address is Fods12 at gmail.com. That's FODDS12 at gmail.com. Thanks once again for listening, and I'll talk to you next time.