Cholesterol is a waxy, fat-like substance that is not essentially harmful. In fact, it is found in and is important for all the cells in your body. Your body needs cholesterol to make hormones, vitamin D, and enzymes that help you digest foods.
Your liver is responsible for making all the cholesterol your body needs. The rest of the cholesterol in your body comes from dairy products and other fats you intake.
Excess intake of fats stimulates the liver to produce more cholesterol, which leads to an increase in LDL or low-density lipoprotein. It is HDL or high-density lipoprotein that is good for cell functioning.
Through this article let’s discuss what is the role of cholesterol in the cell membrane.
What is a cell membrane?
The cell membrane is described to be a fluid mosaic. This is because the structure of the membrane is flexible and fluid, and is also made up of a variety of molecules. There are four main molecules that make up the mosaic structure of the cell membrane.
They are phospholipids, cholesterol, proteins, as well as carbohydrates. Each of these molecules gives the cell membrane unique characteristics depending upon the way the molecules interact with each other. Large reservoirs of cholesterol reside in blood serum in the form of lipoproteins.
These are taken up by cells through endocytosis and recycled into the intracellular pool of cholesterol. Thus cholesterol cycles within as well as in and out of cells using many of these transport functions involving fission and fusion between different membranes.
Because cholesterol has profound physical effects on the membranes in which it resides, it is to be expected that membrane cholesterol also dramatically affects membrane fusion and membrane fission.
What are the roles played by cholesterol?
Cholesterol plays a significant role in the function of the cell membrane, which has the highest concentration of cholesterol, with around 25-30% of lipids in the cell membrane being cholesterol.
Cholesterol modulates the bilayer structure of most biological membranes in multiple ways. It helps to change and adjust the fluidity, thickness, compressibility, water penetration, and intrinsic curvature of lipid layers.
Cholesterol plays a role in membrane fluidity, but its most important function is in reducing the permeability of the cell membrane. Cholesterol helps to restrict the passage of molecules by increasing the density of the packing of phospholipids.
Cholesterol can fit into spaces between phospholipids and inhibit the diffusion of water-soluble molecules across the membrane. The hydrophilic hydroxyl group of cholesterol interacts with the aqueous environment, whereas the large hydrophobic domain, fits in between the C-tails of lipids.
Cholesterol also affects functional attributes of cell membranes like the activities of various integral proteins. Because cholesterol provides rigidity to fluid phase membranes, it is also likely to be effective in countering some of the temperature-induced perturbations in membrane order that would otherwise be experienced by animals that experience varying body temperatures.
Cholesterol contributes to viscous home adaptation (HVA); therefore, more cholesterol is likely to be present in plasma membranes in warm-bodied animals than in cold-bodied animals. This prediction is strongly supported by studies examining cholesterol contents in membranes from endothermic as well as ectothermic animals.
Comparisons of cholesterol levels in temperature acclimated ectotherms reveal either an increase in cholesterol with temperature, no change in cholesterol content, or an increase in cholesterol with a decrease in temperature. These different patterns largely represent tissue along with regional differences in the membranes (membrane domains).
The membrane-specific nature of the response of cholesterol to temperature is likely to arise from
the multiplicity of the effects that cholesterol exerts on membranes, as well as the heterogeneous nature of plasma membranes. These factors enable cholesterol to perform more than a single particular role in the temperature adaptation of plasma membranes in animals.
How does Cholesterol Affect the membrane?
Due to the very small size of the polar headgroup compared to the cross-sectional area of the apolar portion, cholesterol is known to generate intrinsic negative curvature in lipid bilayers. Cholesterol thereby has the potential of promoting highly curved membrane structures such as lipid stalks that are proposed as lipid intermediates in membrane fusion.
Lipid bilayers exhibit resistance towards bending into curved structures that are different from their equilibrium structure. This is expressed in the curvature elasticity and is dependent upon the lipid composition.
Cholesterol increases the bending modulus and therefore the stiffness of fluid membranes, especially when they consist of saturated lipids and are in a state of Lo phase.
Cholesterol modulates the structure and activity of integral membrane proteins through different mechanisms. Cholesterol influences the behavior of membrane proteins in lipid bilayers in several ways. Generally, we distinguish between
(i) global effects of the perturbed lipid bilayer, on membrane protein behavior and
(ii) specific effects of cholesterol binding to define binding motifs on membrane proteins.
The increased order of the lipid acyl chains leads to a reduction of free volume in bilayers when cholesterol is introduced. This increased free volume changes the conformational behavior and shifts the conformational equilibria of membrane proteins in the presence of cholesterol.
These effects have been extensively studied with G-protein-coupled receptors (GPCRs), and most notably, how cholesterol affects the Meta I – Meta II equilibrium in the photocycle of rhodopsin. In other GPCRs, for example, the oxytocin, cholecystokinin, β2-adrenergic, and serotonin 1A receptors, cholesterol is known to enhance ligand binding and downstream signaling.
Cholesterol also stabilizes the structure of the M2 proton channel in the influenza envelope membrane. The length of the transmembrane (TM) domain of the M2 protein is relatively short and prefers relatively thinner (Ld) regions of the membrane, but the amphipathic helix of M2 gets stabilized because of the higher concentrations of cholesterol present in thicker (Lo) regions of the membrane.
To satisfy both requirements, M2 prefers Lo domains, but it may also partition into domain boundary regions where it could help viral budding from the cell membrane envelope. Indeed, both M2 and Cholesterol are essential for the efficient budding of influenza particles from virus-producing cells.
The binding of the anti-influenza drug amantadine in the pore of the tetrameric M2 channel is, however, independent of cholesterol.
Therefore, we know that cholesterol is very significant in maintaining the proper functioning of the cell membrane. However, at the same time, we should make a conscious effort to ensure that we control the increase in bad cholesterol.