Science & Culture: Opening the Door to the Cell

What are cell membranes?

Every human is composed of billions of cells. Cells perform a multitude of important activities, like making energy, digesting nutrients, and managing our immune system. To operate these processes without interference, each cell protects itself with an outer shell called a cell membrane. These shells do a plethora of activities for the cell, including protecting the cell from dangerous intruders, keeping the cell hydrated with enough water, and acting like a post office for incoming and outgoing materials. Cell membranes are composed of fatty molecules called lipids. One common example of a lipid is cholesterol, which is pictured below, but there are multiple types in cell membranes.

These cell membranes have their own “behavior” as they are dynamic environments. One example is that molecules can pass through them and lipid molecules can exchange places with their neighbors. Due to this dynamism, membranes can develop special regions called “lipid rafts.” In these areas, the cell membrane acts like an “unlocked” door as it is notably “more open” to things in your body like hormones and viruses. Because of their behavior, lipid rafts can make cells more vulnerable to diseases like Parkinson’s, Alzheimers, and HIV. These lipid rafts are particularly special as they do not last for a long time, so they can be made and dispersed quickly in cell membranes. In contrast, cells can create and send out signals to other nearby cells through lipid rafts. In other words, they act like an automatic door: they can open and close quickly, only letting in one person before it shuts on the next.

Lipid Rafts – A gateway to the cell

Researchers at Saarland University in Germany have recently published a research article that further investigates the behavior of these lipid rafts. They found that increasing the amount of cholesterol in a membrane makes it more fluid or “unlocked.” These results contradict our traditional understanding of cholesterol, as scientists have previously observed that it “plugs holes” everywhere in the cell membrane. By blocking these holes, the cell membrane is less fluid or “locked.” 

To study lipid rafts, the team used both experiments and mathematical models to explain the results they found. For their experimental platform, the group constructed a synthetic cell membrane using two different lipid molecules. Within these membranes, they placed very small tubes (called Ultra-Short Carbon Nanotubes or USCNT’s) and measured what happens. First, the team calculated a property called the lipid deuterium order parameter, which is a measure of how “unlocked” the membrane can be. They calculated that the membrane was more fluid/”unlocked” around the USCNT when the area had cholesterol. 

In addition, they developed a device which allowed them to experiment with how “unlocked” the synthetic membranes were to USCNT. USCNT’s were sent through a small tunnel of water toward a synthetic membrane, and they looked for them to pass through on the other side. The team used images from a fluorescence microscope (pictured below) and electrical conductance to see if the USCNT passed through. In their experiments, the synthetic membrane with no cholesterol blocked the USCNT’s from passing through as it was “locked.” When the membrane had cholesterol, it was “unlocked” as USCNT’s passed through it. Furthermore, the team measured an electrical current in the tunnel when the USCNT’s passed through. So, the tubes had entered the membrane, made a hole to let the tunnel conduct electricity, and then passed through to the other side! This whole process occurred in a very fast time span (~5 milliseconds)!

Fluorescence image of USCNT passing through the synthetic membrane. The red circle and orange arrow point to the USCNT and the purple arrow points to the membrane [Guo et al., 2020]

In conclusion, the USCNT’s can insert themselves into and pass through the membrane over a quick time span with the help of cholesterol “unlocking” the door.

Why does this matter?

These results directly contradict our previous knowledge of cholesterol’s role in the cell membrane. Instead of “blocking holes,” this article implies that cholesterol “opens” them. This implies that increasing the amount of cholesterol in their synthetic membrane could mimic a lipid raft region in an actual cell. So, these results help explain how these regions work!

Furthermore, this research provides us with a possible narrative of cell membrane behavior. Our cells need to balance how “unlocked” their membranes are, as they need to simultaneously let in beneficial molecules like nutrients while blocking out dangerous intruders like diseases. So, we look to better understand how our cells regulate their cell membrane and protect themselves!

In other words, the cell membrane has a super stressful job; any fault in its behavior can cause the death of the cell. Understanding its behavior as a complex “post office” or a “semi-unlocked door” lets us discover new ways to treat people in medicine. By “unlocking the door,” we can provide beneficial drugs or remove harmful diseases from our cells and ultimately cure people of complications like COVID-19. Cell membranes are the “doors” to health, and research is the key.


Daniel Speer is a PhD student in the Chemistry Graduate Group at UC Davis. He investigates the physical response of lipid membranes to chemical and molecular forces. When you cannot find him in the lab, he’s playing ultimate frisbee in the SF bay area or surfing the coastline.


References

Alves, A., Dias, R. A., Kagami, L. P., das Neves, G. M., Torres, F. C., Eifler-Lima, V. L., Carvalho, C. D. M. S., & Kawano, D. F. (2018). Beyond the “Lock and Key” Paradigm: Targeting Lipid Rafts to Induce Selective Apoptosis of Cancer Cells. Current medicinal chemistry25(18), 2082-2104.

Guo, Y., Werner, M., Fleury, J. B., & Baulin, V. A. (2020). Unexpected Cholesterol-Induced Destabilization of Lipid Membranes near Transmembrane Carbon Nanotubes. Physical Review Letters124(3), 038001.

[Cover image source Guo et al., 2020]

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