Meet the Cell Membrane
Turn on your local radio broadcast or any news channels on the TV and notice how life-consuming (literally) the pandemic is! All that’s running through one ear and out the other are either statistics of available beds, death counts, and linear graphs that depict nothing but an increasing slope.
It can be frustrating to not know what really is going on within our bodies or the true tactics of the national enemy. Why learn about cell membranes? They’re just barriers of the cell that protect it from harm and there’s nothing to study! Biology textbooks tend to overlook countless minor details of the cell membrane, and especially in a time like this, it is so important to combat ignorance and know what is going on in our cells!
Think back to a pre-COVID-19 era, when we were able to travel as we please. Now think about that time your little brother had tried to sneak in an Xbox console through the TSA checkpoint at the airport. The cell membrane is just like that security checkpoint, except it doesn’t exhibit strict guards asking for your birthday or deceiving signs telling everyone to take off their shoes.
Instead, it consists of a phospholipid bilayer, cholesterol, proteins, and receptors. One major similarity between a TSA checkpoint and the cell membrane is that they both are selective. The cell membrane is often described as selectively-permeable because it is the pickiest constituent of the cell; it allows only certain substances to enter and exit.
The Phospholipid Bilayer
Coins and lizards are not the only things that have heads and tails. The cell membrane or plasma membrane consists of a double layer of phospholipids. Each phospholipid has one head made up of glycerol and phosphate, and two tails made up of unsaturated and saturated fatty acids. The head is known as the hydrophilic (water-loving) region, while the tails are known as the hydrophobic (water-fearing) region.
Cholesterol is the second type of lipid present in most cell membranes.
Misconception: People often characterize cholesterol as the thing that clogs arteries. In this context, cholesterol is a fundamental building block of a cell membrane.
Not only does cholesterol exhibit the same “dual attraction” (attracted to and soluble in water) like phospholipids, it regulates the fluidity of the cell. At lower temperatures, it prohibits certain interactions between fatty acid chains that make up the membrane. By creating more gaps in these chains, the cell will become more permeable, allowing more solute to enter the cell than usual. The flexibility of the cell membrane is also important for cell growth (maintaining a normal surface area-to-volume ratio) and mitosis, a.k.a. cell division.
See? Cholesterol ain’t so bad!
Transportation and Permeability
The cell membrane tends to reject substances that are identified as suspicious and harmful:
Does this ring a bell?
That’s Gandalf the Grey from J.R.R. Tolkien’s the Lord of the Rings. The cell membrane is the cellular replica of the wizard icon.
Misconception: Cell membranes are not to be confused with mucous membranes that are tissues formed by layers of cells.
Toxic ions, acids, and alkalis encompass the cell, but thanks to this highly selective membrane, the cell is often protected. The membrane also monitors the transport of essential nutrients entering the cell and waste products exiting the cell.
Transport can be labelled as either passive or active. The major difference between the two labels is that active requires energy while passive does not. Active transport is like going uphill on a hiking trail; it requires energy to go against its gradient (or incline), in a process where the protein moves from an area of lower solute concentration to an area of higher solute concentration.
In contrast, passive transport or facilitated diffusion is like bombing a hill on a skateboard, where solutes move from regions of higher to lower concentration level with the help of a protein carrier. Examples of these processes include a red blood cell using passive transport to transfer glucose across membranes, as opposed to epithelial cells depending on active transport of glucose from the gut.
epithelial: relating to the intestines (in this context)
The Nernst and GHK-flux Equation
You may be stratching your head at this one. How could there be a way to combine math and cell membranes?
The answer is simple: electrochemistry.
The Nernst equation is used in electrochemistry to determine the magnitude of the electrodiffusion of a cell.
electrodiffusion: the diffusion of charged particles under the influence of electricity
Voltage and concentration gradients influence the electrodiffusion of a cell, therefore, the Nernst equation is used to determine this value which is called the Nernst potential. Think of this value as you may think of a “standard form” of a certain mathematical concept.
concentration gradient: gradual change between concentrations of solutes in two different regions
The Nernst equation is used under ideal conditions, where there is no net current flow of ions (thermodynamic equilibrium) at the electrode (electricity conductor) surface and when membrane potential = Nernst potential.
The Nernst equation requires one to know the concentrations of an ion (with a charge of z) inside and outside the cell membrane:
R is the ideal gas constant which has a value of 8.314472 (joules per Kelvin per mole)
T is the temperature (Kelvin)
F is Faraday’s constant which has a value of 9.6485309 * 10⁴ (coulombs per mole)
Unfortunately, the real world does not promote ideal conditions. In physiology, active ion pumps such as the sodium-potassium pump disrupt equilibrium, so in order to calculate electrodiffusion, the Goldman-Hodgkin-Katz (GHK) flux equation is used.
It determines the resting membrane potential, which is the electrical potential difference across the cell membrane of an unstimulated cell (a system that is not at equilibrium). An example of an unstimulated cell is a neuron that has the potential to be in an “excited” state, but when it is not in this state, it is considered to be “at rest.”
New variables:
Em is the membrane potential (volts or joules per coulomb)
Pion is the relative permeability for that ion (in meters per second)
[ion]out is the extracellular concentration of that ion (in moles per cubic meter
[ion]in is the intracellular concentration of that ion (in moles per cubic meter)
Let’s see this GHK-flux equation in action!
Because the question prompts that we are dealing with K+ and Na+ ions, we need to plug in the known concentrations and relative permeability from the data table:
Now we know the exact value of the membrane potential.
And why is this value important?
It is the numerical value attached to neurons or muscle cells “at rest.” It calculates the difference in electric potential between the interior and the exterior of a biological cell. Scientists use these millivolt values to determine the difference between an unexcited or excited cell, or possibly a damaged cell that is supposed to have a certain mV range (typically –40 mV to –80 mV).
In this example, K+ and Na+ ions are specifically used because in all animal cells’ membranes, there exists an enzyme called the Na⁺/K⁺-ATPase (sodium–potassium adenosine triphosphatase, also known as the sodium–potassium pump).
Proteins
Like I mentioned earlier, the plasma membrane is extremely picky. Cell membranes pick off any green on their plate. What I mean is that they are so picky that they repel essential macromolecules and ions that must be imported and exported by the cell in order to live.
Cells that exhibit a greater number of proteins, whether they are living on the surface of the membrane or internally tucked under the membrane, tend to have higher metabolic activity. Proteins that exist outside the cell are called extrinsic proteins or better known as peripheral proteins.
Peripheral proteins are held in place, embedded on the surface of the membrane by hydrophobic, electrostatic interactions (ionic bonds or calcium bridges). Think of these proteins as extroverts wanting to socialize and have some fun!
The cytoskeleton, a system of fibers temporarily anchors and prevents these proteins from touching the hydrophobic space of the bilayer. To further prevent from being sucked into the membrane, the proteins expose a surface of hydrophilic regions.
The functions of the peripheral proteins include: communication, molecule transfer, support, and catalysis. Examples of peripheral proteins: spectrin of erythrocytes, cytochrome C and ATPase of mitochondria and acetylcholinesterase in electroplax membranes.
In contrast, there exists a second class of proteins called intrinsic or integral proteins. They are embedded within the phospholipid bilayer and do not appear on the surface of cells. Think of these proteins as the introverts of the group; they rarely interact with the outside world.
Some integral proteins are structured as open channels, others characterized as facilitators (passing through a lipid screen), pumps (diffusion by force), or receptors. Macromolecules such as carbohydrates are too big to diffuse through the membrane, so they are broken down into smaller particles and are secreted via exocytosis. Examples of integral proteins: drug/hormone receptors, antigen, and rhodopsin. The funny thing is that hormones actually make us feel lonesome and embarrassed of being so introverted! The irony is real…
exocytosis: the transport of material out of a cell by means of a sac via secretion of the cell
Receptors
Now that we have touched upon the topic of proteins, let’s move onto receptors. Chemical signals are released by neighboring cells in small volatile, soluble molecules called ligands. This signal molecule will match with a specific receptor on the cell’s surface (but do not travel across the membrane). There are three types of receptors: ion channel-linked receptors, G-protein-linked receptors, and enzyme-linked receptors. All these receptors convert the chemical signal into an intercellular signal.
Misconception: People think receptors are completely different from proteins. Receptors are a special class of proteins that bind to ligands!
Ion channel-linked receptors allow sodium, calcium, magnesium, and hydrogen to pass through.
G-protein-linked receptors activate the G-protein, a peripheral protein. These proteins communicate either with ion channels or enzymes. G-proteins, once bound to the correct ligand, split into two subunits and activate other proteins on the membrane.
Enzyme-linked receptors can be enzymes themselves or may interact with an enzyme to set off a chain of events within the cell.
Virus Behavior
We all think we know so much about the coronavirus. Please continue to encourage others to wear masks, but also encourage others to learn about the interactions between a virus and our body.
Viruses need a host cell to reproduce because they are protein shells encapsulating DNA or RNA. Viruses have the ability to mutate so it can properly bind to cell-surface receptors and eventually evolve to affect other species of hosts.
An excerpt from www.drugtargetreview.com explains how SARS-CoV-2, the name of the virus that causes COVID-19 gets into a normal, healthy cell:
Researchers have used cryogenic electron microscopy to show that coronaviruses enter human cells through an interaction with angiotensin-converting enzyme 2 (ACE2).
Scientists exploring how coronaviruses like COVID-19 infect human cells have shown that the SARS-CoV-2 spike (S) glycoprotein binds to the cell membrane protein angiotensin-converting enzyme 2 (ACE2) to enter human cells.
COVID-19 has been shown to bind to ACE2 via the S protein on its surface. During infection, the S protein is cleaved into subunits, S1 and S2. S1 contains the receptor binding domain (RBD) which allows coronaviruses to directly bind to the peptidase domain (PD) of ACE2. S2 then likely plays a role in membrane fusion.
The Cell Membrane Chip: An Emerging Technology
Obviously, we have to act now. How are we able to apply this knowledge to beneficial technology? Are there any underrated scientists out there searching for the answer? In fact, yes, you can create something incredible with simple known facts of the cell membrane and implement them into a bigger project:
Researchers from the University of Cambridge, Cornell University and Stanford University have created a chip that mimics the structure, behavior, and functions of a cell membrane. It can mimic from plants’ cell walls to animal cells’ membranes. The chip’s primary goal is to protect the cell from COVID-19 viruses by monitoring the membrane’s ion channels.
The research team is in the process of also creating a sensor that monitors the cell membrane’s structure, fluidity, and control of ion movement.
The research team is funded by the United States Defense Research Projects Agency (DARPA) and have approved of the testing of the device’s effects on drug candidates.
“‘With this device, we are not exposed to risky working environments for combating SARS-CoV-2. The device will speed up the screening of drug candidates and provide answers to questions about how this virus works,’ said Dr. Han-Yuan Liu, Cornell researcher and joint first author on both papers.”
Debrief
Well, after reading all the 2163 words on this article, what did you learn? Has your now-fried brain stored these key takeaways?
- The selectively permeable cell membrane is made up of a phospholipid bilayer alongside receptors and proteins
- This bilayer has nonpolar and polar regions, serving as the habitats for different proteins that either integral or peripheral proteins
- The electrodiffusion of a cell at thermodynamic equilibrium can be calculated using the Nernst equation
- The electrodiffusion of a cell (i.e. muscle cells, neurons) “at rest” can be calculated using the GHK flux equation
- Membrane proteins have many functions: transporting ions, acting as enzymes, or mechanically supporting the membrane
- Receptors bind to ligands and by doing so, the cell can receive chemical signals from the external environment
- Viruses need host cells to reproduce and SARS-CoV-2 particularly targets the protein ACE2 in order to enter a cell
- Emerging technologies like the membrane chip are funded/supported by DARPA and are bound to be a success!
