Kubrick And Cholesterol

Figure 1

You may wonder what the greatest filmmaker in history has anything to do with that greasy little molecule – apparently the only common aspect is that both have something to do with Private Gomer Pyle (Figure 1). Here, I want to discuss an interesting concept about the cell membrane – ‘membrane fluidity’, and how cholesterol interacts with the membrane in different ways.

Membrane fluidity is defined as the viscosity of the lipid bilayer in either a cell membrane or a synthetic membrane. This property is important because it affects the lateral diffusion of the proteins molecules within the membrane bilayer, which is something based on the fluid mosaic model of membrane structure.

Figure 2

At physiological condition, the presence of cholesterol will decrease the membrane fluidity and hence increase the stability of the membrane bilayer (Figure 2). Because the structure of cholesterol is a rigid steroid system, it will interfere with the lateral movement of the fatty acid tails on the phospholipid molecules, and the membrane is therefore stabilized as a result. Nevertheless, a certain level of dynamic interactions is still present in the physiological range.

Yet, when the temperature of the system changes, the story ceases to be simple. This is a relevant point because the whole idea of membrane fluidity not only works in living things, but also for systems generated in vitro. That means the temperature is not necessarily in the physiological range, and it will be interesting to see what cholesterol will do to the membrane bilayers at different temperatures.

Cholesterol is actually a bidirectional regulator for membrane fluidity. At low or high temperature, its presence on a membrane bilayer will lead to opposing effects. 

At low temperature, molecular motions are restricted and the phospholipid molecules have limited motion, thus they are 'frozen out' and appear in a solid-like phase on the membrane (or 'gel-phase' as some may put it). In this case, the introduction of cholesterol will increase the fluidity of the membrane, making the phospholipid molecules more mobile as a consequence.

Figure 3

Thus, cholesterol is a bit like Barry Lyndon from the Stanley Kubrick film here (Figure 3). Barry, an underdog from the 18th century, was a party-crasher to the aristocratic class in his era. These rich guys only conformed to the rules and did not want to stand out from the crowd so as not to lose the prestigious status, as if in a form of stasis. The introduction of Barry to the upper class would certainly destabilize that, as seen in Figure 3.

On the other hand, when temperature is high, there are a lot of molecular motions, and the phospholipids are moving a lot on the membrane and the bilayer assumes a fluid-like phase. The introduction of cholesterol will decrease the membrane fluidity and stabilize the membrane bilayer.

Figure 4

Now, cholesterol looks more like Sergeant Hartman from Full Metal Jacket (Figure 4). No matter those new recruits are hippies, fanboys of Dennis Hopper, or still on a trip of LSD, Sgt. Hartman would certainly to whip up some discipline from these kids, or gut-punch any of them to put them in the right place, in a geometry very much like a ‘bilayer’.

For all membrane systems, there is a characteristic transition temperature, where the bilayer will change from a gel-like consistency to the fluid-like consistency (Figure 5). The value depends on the exact chemical structure of the types of phospholipid in question.

Figure 5

One thing for sure, though - no matter there is another war or not, Ann Margaret will probably not come anyway!

by Ed Law

6/10/2018

#CellMembrane #MembraneFluidity #Cholesterol