 So while a lipid bilayer is hydrophobic on the inside, it's not pure oil. If I draw various components here as a function of the position, you can actually determine this in particular from neutron experiments and small angle neutron scattering. You see that you have lots of hydrocarbon CH2 groups here in the interior, so CH3 groups in the middle, and in this hydrocarbon region that has a thickness of maybe 30 angstrom or so, 3 nanometers, there is no water whatsoever. It's completely dried up, and that makes sense because a single water molecule can't form a single hydrogen bond in there. And then as we're getting further to the head groups here, you start having some of these phosphates and choline groups, the carbonyl groups, that's the top of those fatty acids, and then eventually out here you're starting to get the entire water face. Some water molecules will be bound fairly strongly to these head groups, and eventually of course you have the pure water. This part and that part is going to be very good at interacting with the electrons, in particular those phosphates. The phosphorastoms, they have a ton of electrons and that's going to mean that they show up very strongly on micrographs. And if you're a really good experiment, what you do is that you would take a cell and then you would either freeze fractured or cut it in very thin slices. Then you can get that to show up in an electron microscopy experiment. So this is actually not a simple image on a pure lipid bilayer, but it's a far higher resolution image than I showed you on the previous slide. This has been produced by my colleague Lars Norlein at the Karolinsk Institute, and it's actually an image of the part of the core of the horny layer in skin, the stratum corneum, and where that is being formed. And what you're seeing here, these lines corresponds to individual patterns of head groups, and from the spacing here you can actually determine how thick they are. Related to the company I spoke about that I had a couple of my students and postdoc studying permeation through skin, and you can see the length scales here. But at this point, I think it's time to revisit the idealized picture of the membrane versus the real world. I'm going to start to show you an image that might be a bit corny, but I think it's a beautiful illustration. So you won't have the speaker voice here, but if we take a cell and zoom in on it, on the surface of the cell you're going to have a ton of lipids, and eventually we reach the molecular scale. Now in contrast to proteins, it's important that this is an extremely flexible membrane. That's the whole point of liquids. They can move, I can push my skin. But it also means that if you push it hard, you're not really going to break the membrane, or you might break it locally, but they will reform, they will self heal, and that's an exceptionally important property of lipid to help them compartmentalize various parts of the cell. Because again, if they broke easily, our cells would leak. Now in a real membrane, it's not just lipids. You have cholesterol, the small grape parts there, they will make some of our membrane stiffer. Plants might have lots of them. You will also have sugars, you might have proteins in it. So in principle, this is a relatively complex component, far more complex than the simple images I've shown you this far. But there is one shortcoming, both of this movie and most of movies and drawings that you might have seen in textbooks. Do you see how they've drawn all these lipids with perfectly parallel tails? That's not true. That's not what a membrane looks like. A real membrane would rather look something like this. This is based on a molecular simulation. In fact, one of, I think, I might even have been me carrying this out, or one of my students a long time ago. Do you see the interior here that it's completely chaotic? That makes sense if you think about entropy, because each of these hydrocarbon tails, they can be either in a cis or a trans conformation, right? What is the probability, the pure probability that all of these would be in trans conformation so that they would be completely stretched out? It would pretty much just be one single microstate. It would be exceptionally disadvantages from an entropic point of view. So the whole reason why this does form is that by putting all the hydrocarbon tails together, that means that they have lots of freedom. There is no water perturbing them. They can pack reasonably efficiently, but they are also very free to move. And that's going to be a strong reason why you see there is not a single water entering. They want to maintain their hydrogen bonds while the carbons maintain their freedom. And that's pretty much the reason why membranes are stable. Water want to be out here, the hydrocarbon want to be out here. Will water ever get through? Well, to first approximation I would say no, because for a single water it's so expensive to break all its hydrogen bonds, it's never going to happen. But if we take another molecule, a hydrophobic molecule, say as an oxygen molecule O2, that's a gas. And the oxygen itself doesn't need any hydrogen bonds. In fact, oxygen molecules are quite hydrophobic. So oxygen molecules will be able to diffuse straight through this membrane, which is what they do for instance in red blood cells. So that's going to be important. It's a membrane, but it's not the brick wall. It's semi-permeable. It's permeable to some molecules, in particular non-water soluble ones, while it keeps water out. If it did not keep water out, I would be dead, because everything inside my cells would immediately leak out. In fact, that's a fairly deep result in physics. To be able to maintain any type of life processes, chemical processes at all, you need an anisotropic system and you need some sort of gradient. We need to be able to maintain higher concentrations of some things on the inside and lower concentrations of other things on the inside, so that we can keep processes going. Otherwise, it would be like taking all the components in my body and mixing them up in a single bone. And that would certainly lead to some chemical reactions, but those chemical reactions would cease after a few minutes or so. And when those have ceased, there would be nothing more that could sustain life in that process. So membrane proteins are, sorry, membranes are important for a number of reasons. They create a compartmentalization. I'll try to do all that here. Compartment, meaning small building blocks, literally the cells. And without those compartments, we would not be able to sustain any processes. It's also a scaffold. You remember the last picture that there were things bound in the membrane, for instance, sugars that might be receptors, anything that's on the surface of the cell. This is literally going to be the background that will hold them. Otherwise, we could not expose them on the outside of the cells. It's a barrier, but it's not a normal barrier. It's a semi permeable barrier. So it will let some things through. And that in particular means that it can transport things in and out of the cell. It will be related to signaling. Signaling is kind of also transport, but by transport here, I mean actual chemical molecules such as oxygen. Signaling might mean that a neighbor cell might tell my cell to do something. And that will signal we'll somehow have to go through the membrane, even if I'm not necessarily moving any molecule along. They're in general intracellular interactions and everything. And it's also going to be very important to energy transduction. So energy going in and out of the cell. Let's look at a real membrane though, because the one thing that I've forgotten here are the membrane proteins that were supposed to be the topics of today's lecture.