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Fats have always had a bad reputation in the scope of health. Eating greasy food and doing little exercise, which promote fat accumulation, are deemed poor life choices that will lead to either obesity, cardiovascular disease or both. And while I am not advocating for any of these two activities (in fact, you can read about the benefits of exercise here), to truly live a healthy life, one must intake around 20-35% of daily calories from fat. How can this be? Lipids (the slightly more technical term for fats) have been absolutely indispensable molecules since the beginning of life on Earth. The ability to create an enclosed space with a different chemistry inside of it than outside is one of the main reasons why there is so much diversity on our planet. The lipids made it happen by assembling into bilayer vesicles.

Thanks to our understanding of these lipid membranes, science has allowed for the artificial creation of similar structures in vitro that can be used in medicine with therapeutic implications or as diagnostic tools. By enhancing nature’s own design, we are now able to deliver drugs more efficiently and assess the health of patients by taking advantage of the properties of lipids.

Description of membranes

As was hinted above, the membranes that we find in our cells (animal cells) are made up of phospholipids arranged into a bilayer. Because of their chemistry, phospholipids have a polar and a non-polar side. This is relevant because, in the membrane, the non-polar tails of two of these lipid molecules are in contact, while the two polar heads point outwards, ultimately influencing its properties.

Why do the two polar heads not interact instead?

Bear in mind that most of the cytoplasm is made up of water, while the substances surrounding cells tend to be aqueous solutions too. Therefore, the heads of the phospholipids are the only fragments that can be in contact with those environments, since water is also a polar molecule. The non-polar tails are long hydrocarbon chains that are non-soluble in water and by interacting with each other, they create a region of hydrophobicity.

Cholesterol and proteins

Another lipid that is commonly found in membranes is cholesterol. This is also an amphipathic (containing polar and non-polar sides) molecule, like phospholipids. Thanks to its wedge-like shape, it creates disruptions between the tails of the phospholipids to make the membrane more fluid at cold temperatures and more rigid at high temperatures.

You can see this description of a membrane depicted in the following diagram.

As you may have realized, there are other components within the membrane that are not lipids. Indeed, several proteins can traverse or lay above or below the membrane and each one serves a specific purpose. Some of these proteins may be channels or transporters to carry molecules into or out of the cell, some may be receptors that are activated by a signal and carry out responses, others may be there for structural reasons, such as adhering two cells to each other to create tissues. This diversity of proteins, among other features, is what makes biochemistry such a rich area of knowledge.

Hydrophobic effect

If you are still interested in knowing more about why the lipids adopt this conformation instead of forming a three layered sheet or micelles, read this section. If not, you may skip ahead.

The lipid bilayers form spontaneously because the interaction of the hydrophobic tails in the aqueous solution is thermodynamically favorable. Before unpacking what this means, it is helpful to go over the concept of entropy, also referred to as disorder or chaos. In general, the entropy of the universe tends to increase (this is the Second Law of Thermodynamics). Therefore, any process that results in a positive change in entropy, will be thermodynamically favorable.

In the case of the lipids in water, it seems counterintuitive that an ordered array of phospholipids would result in greater disorder. However, it is not the entropy of the lipids that is increasing, but the entropy of the surrounding water molecules that experiences this change.

This is called the hydrophobic effect. When a lipid molecule enters in contact with water, it immediately becomes surrounded by water molecules that form a cage around it to minimize its interactions with other polar molecules. Forcing the water molecules into this ordered structure decreases their entropy. Once more lipids are added, they will form hydrophobic interactions between themselves and some water molecules will be freed from adopting this cage conformation. Altogether, the vesicle-like lipid bilayer is the structure that allows for the greatest hydrophobic effect to take place and thus is favored in any situation.

Medical applications of membranes

Now that you have a clear idea of what a membrane is and how it is important for our survival, let’s consider some of the ways that they are being used or altered in medicine to help improve our quality of life.

Liposomes

Liposomes are small circular vesicles made up of lipid bilayers. These are useful because they allow storage of other kinds of molecules inside of them, guaranteeing their protection, until they encounter another lipid structure, at which point they will fuse and release their contents. Does this sound familiar?

The current mRNA vaccines against COVID-19 work in this fashion. A series of lipid nanoparticles (LNP) containing the genetic message to synthesize the spike protein are injected into our arm muscles so that when these fuse with our cells, the ribosomes can begin production immediately. Although there are slight differences between liposomes and LNP the principles behind them are the same.

Just like these liposomes can be used to administer vaccines, they can also be used for a variety of other treatments. An advantage of using this delivery method is that they can be modified by attaching proteins that bind specifically to certain tissues, making the administration of the drug more precise and effective. Furthermore, the liposomes tend to concentrate in areas with high blood flow, which tend to be solid tumors and sights of inflammation, facilitating the targeting of those kinds of cells.

Diagnostic devices

Lipid membranes can be used to diagnose certain environmental conditions or biochemical alterations by taking advantage of their electrical conductivity. Biosensors made out of membranes with certain polymer additions and the correct set of electrodes can help detect alterations in certain conditions. One example of this is the measurement of real time fibrillization of amyloid-beta proteins, one of the main causes of Alzheimer’s disease.

Conclusion

You have now seen some medical applications of lipid membranes and their advantages. There are still significant obstacles to overcome for both liposomes and membrane diagnostic tools to become more widespread, but those have not been mentioned here. Instead, consider how amazing it is that from previous studies of membrane structure and function, we are now able to enhance a naturally existing design to suit our purposes of drug delivery or diagnosis. This exemplifies one of the pillars of science which is the idea of discovery and invention. Once we know the secrets of the natural world, we can apply them to keep improving our health and advancing technology.

Bibliography

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Trinity College Hartford
Biochemistry

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