Lipid and membrane biochemistry

Lipids allow our bodies and our cells to compartmentalize, and they also themselves have different properties and modifications that allow them to interact with proteins and other molecules, etc. Different membranes (e.g. plasma membrane vs. nuclear membrane vs. mitochondrial membrane vs. endoplasmic reticulum membrane) have different lipid compositions. They are all made up of phospholipids, but they have different proportions of different ones.  
 
In a bit more detail, phospholipids are what we call “amphiphilic” - they have parts that water likes (hydrophilic parts) and parts that water hates (hydrophobic parts). The hydrophilic parts of phospholipids are phosphate-containing “heads” (which is where a lot of the variation comes from) and the hydrophobic parts are hydrocarbon “tails” (long chains of carbon & hydrogen). The phospholipids in our membranes have 2 tails, so they have a sort of rectangular shape.  
 
If you stick them in water, the water molecules are going to gang up on them, flocking to the hydrophilic parts (as well as clinging to other water molecules) and running away from the hydrophobic parts. This leaves those hydrophobic tails left with nothing to hang out with but one another. But their rectangular shape makes this awkward. The solution? Take inspiration from a sandwich! The phospholipids form a bilayer membrane where the heads take on the role of the bread and the tails the peanut butter.  
 
Speaking of butter, sorry I didn’t explain more before but the term “lipid” is basically a broad category that encompasses fats, oils, waxes, and other largely “nonpolar” hydrophobic molecules.  
 
Also speaking of butter, the membrane is fluid. Individual lipids can move around within the layer (leaflet) they’re in - but they need the help of proteins called flipases in order to swap to the other leaflet. This allows there to be distinct asymmetry in membranes with the two layers being different. Proteins can also move around in the membrane (though not quite so easily as the lipids), leading to a concept called the “fluid mosaic model” where you have a sort of sea of lipids that proteins live & move around in. And often the proteins hang out in groups - this potential for localization, using the membrane as an organizing center is one of the virtues of membranes.  
 
When we think about membrane proteins there’s a tendency to focus on “main membrane” - the plasma membrane. I know I have this bias myself. But don’t forget those other ones. And don’t forget that the lipid composition (what proportion of the lipids have which head, etc.) can matter greatly. That being said, when we study membrane proteins in vitro (in a test tube or other artificial environment) we typically make simplifications that make things more generic and less realistic. Such as by using those detergents.  
 
So, what is a detergent? It’s an artificial soap. And what’s that? Basically, it’s another type of amphiphilic molecule a lot like a phospholipid, but with a single tail. This makes it more conical than rectangular so it’s less awkward to arrange themselves in a single, spherical, layer. So this is what they do when you stick them in water. They form those liquid-filled bubble things called micelles, where their hydrophilic heads are on the outside, facing the water, and their hydrophobic tails are in the center (this is also where hydrophobic gunk hangs out when you’re using soap or detergent to wash things).  
 
Since detergents “look” like phospholipids and have a lot of the same properties, they can elbow their way into phospholipid membranes, disrupting them and picking up some proteins which they then drag into their micelles. And this offers you a way to extract membrane proteins from membranes. They’re still hard to purify and keep happy though, so scientists often try to avoid all this. Instead, if they want to study membrane proteins outside of a cellular context they often express (have cells make) and purify just the hydrophilic inside (endodomain) or outside (ectodomain) parts.  
 
That can be good enough to study things like binding affinity, but you lose a lot of information. A somewhat more realistic environment comes from using lipid nano discs, which are kinda like bilayer lifesavers surrounding proteins. These are frequently used for the structural study of individual membrane proteins or complexes (e.g. via single molecule cryo-electron microscopy (cryoEM)).  
 
note: I have huge respect for people who study membrane proteins. I worked with them during a lab rotation in grad school and man it’s hard! never got those nanodiscs working… but anyways… 
 
More about membrane proteins: bit.ly/membran... & • Membrane protein bioch...
More about lipids: bit.ly/amphilp...
more about all sorts of things: #365DaysOfScience All (with topics listed) 👉 bit.ly/2OllAB0 or search blog: thebumblingbioc...