Phospholipids in Cell Membranes

00:01 Here, we have a membrane.

00:02 Most of this is gonna be pretty familiar to you.

00:05 We'll just go through this very quickly.

00:07 So, a lipid bilayer provides a barrier and an interface from the outside world, which is top, and the inside or cytoplasmic world, which is bottom.

00:18 The lipid bilayers formed of amphipathic molecules.

00:23 Amphipathic meaning that there is a phospholipid, they're phosphated, head group that is charged, and is hydrophilic.

00:33 And that faces towards the outside world and towards the inside world where we have mostly water. And in between, we have lipid tails.

00:41 Those little legs sitting in between.

00:44 That provides a barrier to the diffusion of most things.

00:49 So, it allows us to have a membrane.

00:52 And these will spontaneously assemble.

00:54 If I just take all various lipids -- phospholipids, sorry, with a phosphate head group and a lipid tail, shake them up in a bottle of water, they will spontaneously form into little spheres, forming the lipid bilayer just like you see that.

01:08 Okay, except that in living systems, it's more complex.

01:12 Of course, it is. Otherwise, it would be too easy.

01:14 Complexity comes from the membranes are not symmetric and they're not uniform.

01:21 What do I mean by that? Well, so you -- the colors of the various balls representing the phosphate head groups on these phospholipids are different colors.

01:30 Not randomly different colors, but different colors by design.

01:34 So, the phospholipids that face towards the outside world tend to be dominated by phosphatidylcholine, sphingomyelin, and a few others.

01:43 The ones that stays in the inside world tend to be predominated by phosphatidylserine and phosphatidylinositol.

01:50 So, there are -- there's an asymmetry, and top and bottom actually makes a difference.

01:56 Not only that, but it's not uniform.

01:59 So, if I just have those things in the membrane, they would laterally diffuse and wander around, and they would be a uniform distribution.

02:06 In fact, we have areas that form distinct domains, and what's in the box right there is a lipid raft.

02:13 And it's mostly sphingomyelin.

02:15 It has some other proteins in it, but that lipid raft is gonna be important for certain functionality.

02:21 So, the membranes are actually organized already.

02:24 It's not random. They're organized in such a way that certain lipids face in and certain lipids face out, and they are also organized into domains.

02:34 Okay, let's walk through some of these.

02:36 So, the first one that's highlighted is phosphatidylcholine.

02:39 Next up is sphingomyelin. Next up is cholesterol.

02:44 Cholesterol is actually not a phospholipid. Cholesterol is cholesterol.

02:48 Serine-based structure. And it is invested within the membrane somewhat randomly but will provide functionality in terms of fluidity of the membrane.

03:00 So, the more cholesterol you have, the more fluid the membrane may be.

03:06 Phosphatidylinositol.

03:09 So, the little blue balls on the inner phase and phosphatidylethanolamine, little green balls on the inner phase, and it's got that negative charge.

03:18 In fact, that negative charge may be important because it allows positively charged proteins and other molecules to bind to the interface of the membrane.

03:26 So, there is method to the madness here. Other structures that are present.

03:30 So, glycolipids.

03:32 You've already noticed all those hexagons attached to a phospholipid group.

03:37 We'll those hexagons are various kinds of sugars.

03:40 Galactose and manose and an acetyl glucosamine, they're a variety of sugars.

03:46 And they make these long, complex structures that allow cell-cell interactions.

03:52 Those sugars interact with proteins that bind sugars on another cell type.

03:57 So, glycolipids and glycoproteins will be facing towards the outside world because they're involved in interactions. Lipid rafts.

04:06 I already mentioned that this is an important little area.

04:08 We will come back to this in a subsequent topic discussion when we think about a process called potocytosis or cell sipping.

04:16 And cell sipping occurs at lipid rafts where we invaginate to form little, tiny lacunae, little gaps called caveolae.

04:26 And that is a mechanism by which we can take up certain elements of the outside world, but we can also regulate things that happen to fall into the lipid raft domain.

04:36 Phosphatidylinositol. Phosphatidylinositol is actually there on the inner phase because it is an important secondary signal molecule.

04:47 We will see pathways that will lead to the cleavage of the phosphatidylinositol into inositol triphosphate and diacylglycerol, which are important intracellular second signals.

04:58 So, by having that phosphatidylinositol on the inner phase, we've got a signaling molecule ready to go. That makes sense. That's cool.

05:06 And then, phosphatidylserine. Most of the time, it sits on the inner phase.

05:10 And it's a net negative charge, we already talked about that, but it's also a really important molecule, phospholipid, involved in the senescence of cells in apoptosis.

05:22 And you see there in the red box, it says an "eat me" signal, and it's like, "What?" Well, yeah.

05:27 If the phosphatidylserine which normally lives on the inner phase flips to the outer phase, that's a signal to any cell going by that this cell needs to be eaten.

05:36 And we'll talk about that on the next slide.

05:40 So, this is an example of membrane functionality.

05:43 On the left-hand side, you see are lipid bilayer with all the various constituency, and you see the glycolipids sticking up there.

05:51 And on the inner phase, we have our green phosphatidylserine balls.

05:56 Those are the phosphate head groups.

05:57 At a slightly lower magnification, we're now seeing the cell.

06:03 That's the thing in the middle.

06:04 That's a cell with a nucleus, and there's an inner rim of green.

06:08 That's the phosphatidylserine on the inner phase facing the cytosol of the plasma membrane.

06:14 Here's another molecule just to make it interesting and more complex, CD47.

06:18 CD stands for cluster of differentiation.

06:22 They're a whole bunch of CD molecules. It's a bad name.

06:25 Just live with it. But basically, CD47 is a "don't eat me" signal.

06:29 And virtually, every cell in our body has this signal saying, "Leave me alone. I'm alive. Don't eat me." But the phosphatidylserine, that "eat me" signal, can override that.

06:42 So, right now, the cell that we have there with the CD47 on its surface and the phosphatidylserine on the inside, is not gonna get eaten.

06:53 But if I have damage to that cell or I have it undergo program cell death, the phosphatidylserine now will flip.

07:01 We will no longer keep it locked into the inner phase.

07:05 It goes to the outer phase.

07:07 And on my little apoptotic bodies in this program cell death, I now have phosphatidylserine on the surface. That's an "eat me" signal.

07:16 That's how we get rid of apoptopic bodies.

07:18 The other molecules that are involved in this equation are just there for your edification.

07:22 Do not memorize calreticulin and complement C1q and CD91.

07:27 Don't, don't, don't. But they're involved in the recognition by macrophages and other cells of the apoptotic bodies.

07:34 And with that phosphatidylserine flipped, an important functionality, it now says "eat me".

07:40 It gets phagocytosed, lysosomes fuse with it, you degrade it, and you never had that cell there before.

07:48 So, this is just an example of why the asymmetry of the lipid is important and kind of an interesting, cute story.

07:54 It turns out that there are diseases where we inappropriately express CD47.

07:59 I mean we don't express it very well, and those cells tend to be a much higher turnover, and there are other cells where we lose the ability, the flipase, to keep the phosphatidylserine on the inner phase, and those patients tend to have premature senescence. Kind of interesting.