In this molecule of the month post we’re going to be looking at dipalmitoylphosphatidylcholine or DPPC – a molecule that few people have ever even heard of, and far fewer have spent years of their life studying intensely. That’s what Phil did in his Ph.D. and it’s about time you heard the story of this molecule. We’ll be looking at lipids in the next few posts, so let’s dive in to these oily, fatty molecules and find out.
If you would prefer a video version of this article, you can watch one here:
What is the difference between this puddle with bits of bone in it and you, a living breathing, walking person?
Cell membranes.
I know that’s not a very funny joke, but it is true – without cell membranes that can compartmentalise and contain liquids that 60% of your body1 that is water is going spalooosh all over the floor. It’s been calculated that 40 litres of fluid is contained within cells2 and that’s a big puddle.
So what is a cell membrane?
Have you ever actually heard of a cell membrane? Perhaps it’s a distant memory somewhere from biology lessons at school. Another phrase that you may have heard is the ‘phospholipid bilayer’. It’s an odd phrase, especially when (from my experience at school at least) it gets mentioned and then forgotten about. I even went back and looked at those revision books with all the ridiculous colours and terrible jokes and boxes everywhere (if you’re a UK student you’ll amost certainly know which ones I mean) and they do a really terrible job of explaining why these membranes are important to talk about. No wonder they get forgotten!
A cell membrane is a layer of chemicals that organise themselves into a strong barrier all the way around a cell. The membrane is like a skin that can keep water, nutrients, genetic information, and anything else the cell needs inside and ready to use. It is also a fluid – it can move and rearrange – so we can distribute proteins and other bits of biological machinery in, on, and across this surface.
More than just being a surface for interesting stuff to act from, though, the cell membrane itself can actually do a lot of useful things for the body! We’ll dive in to some of these below and in the next post. First though, let’s talk about about lipids and one in particular at the end of this post, DPPC.
The molecules that make up the membrane are called lipids. Which major food group do you think they come from?
Fantastic fats
There we go! Everyone has heard of ‘fat’ and ‘fatty’ foods. Well those molecules in your fatty food actually end up being digested and chopped up and recombined into loads of different phospholipids – other types of fatty molecules – that stop us from turning into these puddles. Too much fat is bad for us – that’s definitely and unarguably true – but we need some of it to build these membranes out of.
Photo by Ben Stein on Unsplash
To help us understand how these fatty molecules can help with keeping this water in place, pour some oil into a jug of water. We all sort of intuitively know that these don’t mix, right? That oil will float on top of water. Fatty molecules – oily molecules – don’t tend to mix with water.
But if you pour more water on top of this oil, the water just goes straight through that oil barrier. If we want to make this barrier stronger and keep things out, keep that water in one compartment, we’re going to need to add in some structure.
This is where our phospholipids come in. They naturally organise themselves into bilayers, two layers one on top of the other. They are incredible molecules because they have one side that loves water and one side that loves oil and fatty molecules. The structure of DPPC is shown below – the zig-zag chains with no letters (left) are hydrophobic, repelling water. The bit on the right with a postiive and a negative charge and lots of O’s and an N for oxygen and nitrogen loves water.
Phospholipids are made in your body from all the oil we get from digesting fatty food. Without the right amount of fats from food, we wouldn’t be able to make these layers and problems with health would start popping up all over the place.
“Bye bye” thick layers, “Hi” thin bilayers
The layer of oil you poured on to the cup of water might be a centimetre thick – about the same as the width of your finger from the nail to your fingertip. In this layer there will be around five million (5,000,000) oily molecules3 one on top of the other in even this relatively thin layer.
But considering that a cell might be 50 micrometers across, this layer would be far too thick! We need much, much thinner layers of oily molecules.
The ‘bilayer’ in that phrase phospholipid bilayer you might remember means that the barrier is actually made up of just two layers of phospholipids. The cell membrane is just two molecules thick and stands at around 5 nanometres. That is about 2 million times thinner than the layer of oil we poured onto our jug of water. Pretty thin, huh.
Image credit: https://openstax.org/books/anatomy-and-physiology/pages/3-1-the-cell-membrane
The orange blobs with yellow ‘tails’ hanging down here are individual lipid molecules. Putting loads of them together can make a complete layer like the one in the picture above.
Just how thin is this layer? To put these nanometre thin layers into context, take a look down at your fingernails. In the time it takes you to read this sentence they will have grown by about 5 nanometres.4 Can you see the difference? Fingernails grow at about 1 nanometre per second.
What can we go wrong with cell membranes?
Since the cell membrane needs to behave in a really specific way, and that depends on the lipids that make them up, a small problem in how your body deals with lipids can cause a huge problem.
I’ve got two examples of diseases to show you – one that arises from each end of these lipid molecules. The side that faces out into the human soup, and the side that is trapped inside this cell membrane.
The ‘headgroup’ of lipid molecules – the bit that likes water and interacts with the world outside of the cell membrane – impacts the way that cells behave and therefore we need different lipids with different headgroups in different cells that need to do different tasks.
Gaucher’s Disease
Lipid headgroup issues
Gaucher’s disease is a condition where people lack a certain protein that helps to move around one specific lipid. Lacking this protein is caused by an error in just one section of your genetic code, and so it is passed down through families. Without the biological machinery to move these lipids, they build up. They accumulate. And as they do they cause problems by impacting the way that these cells behave.
This particular lipid is used by cells in your immune system, so the effects are noticed in places associated with the immune system. We’ll see how lipids can impact the immune system in some future posts. Your bone marrow, spleen, liver, and so on. This would be bad enough but unfortunately the prognosis gets worse without treatment leading to complications with your brain and nerves.
Frustratingly, with medicine, we often know exactly what the problem is but it would be impossible to use tiny tweezers to go in and remove the build up of these molecules. Instead, we need to give the patient’s body the right machinery to do it itself. This can be done by synthetically creating the enzyme that the person is lacking and giving that to them. Enzyme replacement therapy is hugely beneficial to sufferers of Gaucher’s disease.
Adrenoleukodystrophy
There is also the section of the lipid that does not face out to the outside, but instead faces inside the cell membrane amongst all the other fatty bits of the molecules. The longer these sections are, the thicker it will make the cell membrane, and in turn harder for things to cross the barrier.
If these lipids start to build up then the cells they are building up in will also change. Here comes the problem – these really long-chain lipids start to build up in the sheath that protects your nerves, myelin. The whole point of this sheath is for electrical insulation, so as this sheath gets thicker, the signals that travel along your nerves can struggle to conduct their way along. Information starts going missing, or arriving late. This has, obviously, disastrous consequences for the sufferer.
So this time, what can we do? The body is not able to sort out the long from the short chains in the fats that we eat. One treatment that was such a novel idea and such a surprise that it completely worked that it ended up being made into a film was to change the diet, but not how you would expect. Instead of reducing the amount of fat, since that the fatty molecules are the issue, but instead to increase fat intake massively. The patient drank olive oil every single day. How does that work, you wonder?
With adrenoleukodystrophy the issue is those long chain fats building up. The body can’t shepherd them around the way that you or I can and these long chain acids can jump into the biological vehicles their bodies use to move lipids. So, the treatment was to crowd out this protein’s “bus stop”, if you’ll allow the analogy, and crowd it out with chains of an appropriate length. Now when the biological vehicle comes along those long chain fats that are causing so much of an issue are out-competed – there are just too many shorter ones there fighting for a seat – so the long chain acids get left behind in that way. Then they don’t build up on the nerves, and the patient’s health is protected.
The film is called Lorenzo’s Oil, in case anyone is interested. It just so happens that the chain length (how long that zig zag section in the chemical structure of DPPC above) in olive oil is 16 carbons long, which is also the length of the chains in DPPC and the most common lipids in the human body. This oil gives the body an abundance of the right length of oil it needs to function properly.
N.B. it probably isn’t a good idea for you to just start drinking olive oil because some bloke on the internet wrote about it being good in one very specific scenario – so put that glass down, okay?
What can we build with membranes?
The image that I showed you of a cell membrane was flat because that’s how it’s easiest to draw them in textbooks. In reality though, if we want to contain liquids it needs to be more like a balloon and wrap all the way around. They’re round, basically.
Vesicles
If we can make something balloon shaped out of the same thing that the body is made of, that gives us a brilliant opportunity to sneak some material into a patient. We can make sneaky envelopes of lipids with medicine inside them and let the body transport these packages to where they need to go. We can change the outside of the envelope by changing the lipids that go inside it, and that’s like changing the address written on the outside. We can change the drug molecules and concentrations inside, that’s the package we are trying to send to a diseased part of the body.
Concentrated, specific, targeted medicine like this could be a massive part of our future medical processes. It reduces waste or damage to other parts of the body and we can deliver much higher amounts of a drug to a specific target this way.
In the image above there are no molecules shown inside the vesicle, but it would be possible to contain many of the other molecules we have mentioned in Molecule of the Month inside one of these lipid packages.
Protective films
There are other parts of your body that rely on protective films – especially all those parts of your body that see the outside world.
Your skin is a particularly hardened cell membrane made up of cells that have died and been squashed and dehydrated, filled with reinforcing proteins, and layered up.
The lining of your nose and mouth are more delicate. They are soft and covered in mucus to help them function. That mucus is really important, especially down deep down in your lungs. One of the problems with lungs is that the material they are made of really likes to stick together. Have you ever got caught in the rain wearing a cotton shirt? It sticks to you and feels gross. If you injure your lungs really badly and have a collapsed lung, this can happen. The insides of your lungs get stuck together, and unfortunately you don’t have the strength in your ribs and muscles to pull them back apart. You desperately need medical treatment. This is called atelectasis.
There is a lipid film that is supposed to line your lungs and keep things fluid and moving. If this film is damaged by an injury, not made yet in the case of premature babies, or reduced by harsh medical treatments like a big operation, your lungs can be prone to sticking together like this. One cause of damage to the lining of the lungs is inhaling foreign substances like smoking or vaping.
Another part of your body that relies on a protective film is your eyes. The coating on the outside of your cornea can get itchy, especially if you are tired, have been staring at screens all day, or are allergic to something.
One common way to reduce this irritation is with eye drops. They simply replace the liquid in your eye and help to keep things hydrated. There are also medicated eye drops that can help to reduce the symptoms of allergy. However – a more recent treatment is to help reform this protective film. You can get eye sprays that contain vesicles. The ingredients might say ‘lecithin’ which is an older term for these lipids. All you’re really doing is forming helpful membranes across the surface of the eye that are perfectly see through, being only 5 nanometres thick, but can help to keep irritants and allergens out.
Dipalmitoylphosphatidylcholine – DPPC
One particular lipid – dipalmitoylphosphatidylcholine or DPPC – is very common. It makes a really good starting point for studying and understanding other lipids. If we can understand DPPC really well then we can use that knowledge as a foundation to understand how the rest of the cell membrane interacts.
The ‘palmitoyl‘ section of the name dipalmitoylphosphatidylcholine represents palmitic acid. DPPC has two of these chains as the oily section of the molecule (the tailgroup). If you want to know more about palmitic acid you can read a previous Molecule of the Month post!
Phil does actually have full models of DPPC but unfortunately he left it in his office when writing this article… He will update this post after his holiday! For now, here’s one of the palmitic acid chains instead.
DPPC pops up all over the place in mammals especially. It has two chains of 16 carbons each and a big phosphate-based headgroup at the other end. Many of your favourite foods will be broken down, digested, absorbed, and recombined into DPPC in your body. Then your cells will build and repair membranes out of this lipid, fine tuning exactly what that membrane should do by adding in different lipids or proteins.
One eye medicine that is commercially available specifically uses DPPC, and many of the vesicles made for medical purposes will start from a DPPC stock, or at least a lipid source that is particularly rich in DPPC.
Using DPPC as a starting point to understand other lipids is what Phil’s Ph.D. was all about – there’s even a whole paper just looking at how we can make it tilt a little bit.5 DPPC is actually a very boring lipid because it is found almost everywhere in humans in large amounts and doesn’t do a whole lot. More interesting lipids have impacts on the body – as we’ve seen with the diseases above – so the later stages of my research were spent looking for differences between really similar lipid molecules. You’ll have to stay tuned for next month’s post to play lipid Spot the Difference!
Footnotes
- Water Science School. (2019) The Water in You: Water and the Human Body. Available at https://www.usgs.gov/special-topics/water-science-school/science/water-you-water-and-human-body (Accessed 17/04/2023).
- Guyton, Arthur C. (1976). Textbook of Medical Physiology (5th ed.). Philadelphia: W.B. Saunders. pp. 275. ISBN 0-7216-4393-0.
- Assuming a molecular length of 2.5 nm based on the length of a palmitic acid chain and a random distribtion of lipid chains within the oil layer.
- Yaemsiri, S., Hou, N., Slining, M.M., and He, K. (2010) ‘Growth rate of human fingernails and toenails in healthy American young adults.’ The Journal of the European Academy of Dermatology and Venereology, 24(4), 420-423. https://doi.org/10.1111/j.1468-3083.2009.03426.x
- Jemmett PN, Milan DC, Nichols RJ, Cox LR, Horswell SL. Effect of Molecular Structure on Electrochemical Phase Behavior of Phospholipid Bilayers on Au(111). Langmuir. 2021 Oct 12;37(40):11887-11899. doi: 10.1021/acs.langmuir.1c01975. Epub 2021 Sep 30. PMID: 34590852.
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