# Structural Biochemistry/Lipids/Lipid Bilayer

Lipid bilayer is a universal component of all cell membranes. The structure is called a "lipid bilayer" because it composed of two layers of fatty acids organized in two sheets. The lipid bilayer is typically about five nanometers to ten nanometers thick and surrounds all cells providing the cell membrane structure. With the hydrophobic tails of each individual sheet interacting with one another, a hydrophobic interior is formed and this acts as a permeability barrier. The hydrophilic head groups interact with the aqueous medium on both sides of the bilayer. The two opposing sheets are also known as leaflets.
The lipid bilayer has unique properties. They are formed in sheet-like structures that contain both a hydrophilic and a hydrophobic moiety. The membrane is composed of lipids and proteins and sometimes even carbohydrates. There are two different membrane proteins in the lipid bilayer. Integral membrane proteins traverse the lipid bilayer and are adjacent to both the extracellular fluid and the cytoplasm of the cell. Peripheral membrane proteins only bind to the surface of the integral proteins and are only on either side of the membrane, outer or inner. Specific proteins on the surface of the membrane mediate different functions. For example, the sodium-potassium pump plays a major role in balancing the concentration gradient between the extracellular fluid and inside the cell. Phospholipid bilayer also has electrical properties which, as discussed with the sodium-potassium pump, allows the transfer of ions through and out of the lipid bilayer.

## Structure

The structure of the lipid bilayer explains its function as a barrier. Lipids are fats, like oil, that are insoluble in water because of its long hydrophobic tails. The hydrophobic interactions among several phospholipids and glycolipids, a certain structure called lipid bilayer or bimolecular sheet is favored. Phospholipids and glycolipids have both hydrophilic and hydrophobic moieties (amphiphilic or amphipathic). Thus, when several phospholipids or glycolipids come together in an aqueous solution, the hydrophobic tails interact with each other to form a hydrophobic center, while the hydrophilic heads interact with each other by forming a hydrophilic coating on each side of the bilayer point radically towards the polar solvent.
This lipid bilayer formation is spontaneous since the hydrophobic interactions are energetically favorable to the structure. The lipid bilayer is a noncovalent assembly. The proteins and lipid molecules are held together by noncovalent interactions such as Van der Waals forces (which holds the hydrophobic tails together) and hydrogen bonding (which binds the hydrophilic heads with water), which help to stabilize the lipid bilayer structure.
Proteins are embedded in the biological lipid bilayer membrane. The mass ratio of the lipid molecules and the proteins that are embedded in them ranges from 1:4 to 4:1. Two types of proteins exist in the lipid bilayer: integral and peripheral membrane proteins. Integral membrane proteins traverse the lipid bilayer. That is, they interact extensively with the hydrophobic region (hydrocarbon region) of the lipid bilayer. Integral membrane proteins interact by nonpolar interactions. Peripheral membrane proteins are usually attached to surfaces of integral proteins; therefore, they are on both faces of lipid bilayer. Peripheral membrane proteins interact with the hydrophilic polar head groups of the lipid molecule. Peripheral proteins bind through electrostatic and hydrogen bonds with the head group of the lipid. They usually bind to integral proteins on the cytoplasmic or extracellular side. However, they can also be covalently attached to the bilayer by a hydrophobic chain.
Lipid bilayer membranes are asymmetric, which means the outside face of membrane is always different from the inner face of the membrane.

## Bilayer Dimension

The diameter of the spherical lipid bilayers starts from 250Å and goes up. The width or thickness of the bilayers is determined by the length of non polar tails. For phospholipids and sphingolipids it has ranges between 16 and 24 carbon atoms. Total width including the group heads ranges from 45Å to 50Å.

## Phospholipid Translocators

Because phospholipids are synthesized from the cytosol side of the membrane, there needs to be a way to move the phospholipid towards the lumen side of the lipid bilayer. Scramblase, a translocator, is responsible for creating symmetry between the two leaflets of the lipid bilayer. As each individual phospholipid is synthesized, they are equilibrated between the layers, known as "FLIP FLOP." With the function of scramblase, it is concluded that the different types of phospholipids are evenly distributed between the two layers, seen in ER membrane.
However, in the plasma membrane, a different movement occurs. Part of the P-type pumps, flippase translocator use the energy coupled with the ATP hydrolysis to flip the phospholipids towards the cytosol side of the membrane. Therefore the bilayer in plasma membrane is maintained to be asymmetric by the flippase. Plasma membrane also does contain scramblase, but as opposed to ER scramblase, the scramblase in plasma membrane is activated only at certain times especially during apoptosis and activated platelets, where its purpose is to promote asymmetry.

## Properties

Because of these interactions, lipid bilayer inherits unique properties. Lipid bilayers have "extensive" properties - they can enclose and form compartments. Lastly, they can also recover quickly if there is a hole in the lipid bilayer due to energetic reasons. However, phospholipids and glycolipids do not form micelles like fatty acids do because phospholipids and glycolipids have two hydrocarbon chains and they are too bulky to orient themselves into a sphere like a micelle. Additional properties of the lipid bilayer membrane include that they are: sheet-like, formed by lipids and proteins (sometimes carbohydrates), are amphiphatic, possess some noncovalent parts, are asymmetric, fluid, and are electrically polarized. Using fluid mosaic models, it can be seen that the bilayer undergoes rapid lateral diffusion, but flip-flop or transverse diffusion proceeds very slowly. There is also a hydrophobic transmembrane alpha helix that passes through the membrane, with the amine component on the extracellular side and the carboxy group on the cytoplasmic side.
Membrane Properties: 1. Form sheet-like structures 2. Formed by lipids and proteins (sometimes carbohydrates) 3. Lipid membranes are amphipatic (have properties that are both polar and nonpolar) 4. Specific proteins mediates membrane functions (proteins can promote permeability of membrane) 5. Non-covalent assemblies (hydrophobic forces keeps membrane together 6. Asymmetric (typically because of proteins) 7. Fluid Structures - phospholipids are constantly moving 8. Electrically polarized - has the ability to isolate/separate charges (EX: used to produce ATP or transfer nervous signals)

## Functions of the lipid bilayer

The most important property of the lipid bilayer is that it is a highly impermeable structure. Impermeable simply means that it does not allow molecules to freely pass across it. Only water and gases can easily pass through the bilayer. This property means that large molecules and small polar molecules cannot cross the bilayer, and thus the cell membrane, without the assistance of other structures. This property of the lipid bilayer balance water and other organic molecules from influx/exflux through the cell and environment.
Another important property of the lipid bilayer is its fluidity. The lipid bilayer contains lipid molecules, and, it also contains proteins. The bilayer's fluidity allows these structures mobility within the lipid bilayer. This fluidity is biologically important, influencing membrane transport.
The function of the lipid bilayer membrane is mediated by the specific protein that is embedded in it. The proteins of the lipid bilayer function as pumps, channels, energy transducers, receptors, and enzymes.

### Liposomes

A liposome, or lipid vesicle, is a vesicle enclosed by a lipid bilayer. Lipsomes are the opposite of micelles in that they are hollow on the inside. Liposomes are important for studying membrane permeability and they can be used to deliver ions or molecules inside cells. It is characterized by a bilayer membrane that creates an outer aqueous compartment and an inner aqueous compartment due to the hydrophilic heads and hydrophobic tails of the lipids, as shown by the figure below.
One of the ways liposomes can deliver ions and molecules to the inside of cells is through sonication of phospholipids. Phospholipids are suspended in an aqueous medium and are then sonicated, after which the phospholipids form closed vesicles. Sonication involves applying sound energy to agitate the phospholipids so that they can create liposomes around the desired ions or molecules in the solution. After the liposomes trap the ions present in the aqueous layer, gel filtration is used to wipe out the excess ions. By measuring the rate of efflux of ions from the inner compartment to the outer aqueous solution, the permeability of the bilayer can be measured. The hydrophobic layer of the membrane isolates ions from coming in-as this would be a very thermodynamically unfavorable process. This process is shown in the figure below using glycine as an example.

## Effect of Lipid Bilayers on Local Aqueous Environment

When the majority of lipids in a bilayer are anionic, they attract cations and repel anions. This will result in a special double layer solution depleted in anions and enriched in cations surround the bilayer. This layer has the ability to change the structure and function of membrane proteins. A sodium/potassium pump driven by ATP in the bilayer pumps potassium into the cell and sodium out of the cell.

## Significance of the lipid bilayer

The fact of lipid bilayer, it forms a basis for cell membrane is very significant in cellular biology. If there were no membrane, there would be no distinction between intra and extracellular compartments. If there were be no cells, there would be no ways to understand how many of the biological and chemical phenomena occur since cells are the basic building blocks of life. Employing such difference between hydrophility and hydrophobicity, albeit simple, has enormous significance and consequences in the field of biochemical studies, if not the life itself. This is also an example of how intricate and fearfully the cells are made to operate to bring life.

## Proteins Carry Out Most Membrane Processes

Proteins are responsible for most of the dynamic processes carried out by membranes. In particular, proteins transport chemicals and information across a membrane.
Membranes and Protein Concentration
Membranes differ in their protein content. Myelin, a membrane that serves as an electrical insulator around certain nerve fibers, has a very low concentration of proteins (18%). Relatively pure lipids are usually sufficient in their insulating properties. In contrast, the plasma membranes, or exterior membranes, of most other cells are much more metabolically active. It contains many pumps, channels, receptors and enzymes. The protein content is usually 50%. Energy-transduction membranes, such as the internal membranes of mitochondria and chlororplasts, have the highest concentration of proteins, usually 75%. In general, membranes performing different functions contain different concentrations and repertoires of proteins.
Proteins Associate with the Lipid Bilayer in a Variety of Ways
The ease with which a protein can be dissociated from a membrane indicates how intinately it is associated with the membrane. Some membrane proteins can be solubilized by relatively mild means, such as extraction by a solution of high ionic strength. Other membrane proteins are bound much more tenaciously; the can be solubilized only by using a detergent or an organic solvent. In this manner, membrane proteins can either be classified as peripheralor integral on the basis of this difference in dissociability. Integral proteins interact extensively with the hydrocarbon chains of the membrane lipids, and they can be released only by agents that compete for these nonpolar interaction. In fact, most integral membrane proteins span the lipid bilayer. In contrast peripheral proteins are bound to membranes primarily by electrostatic and hydrogen bond interactions with the head groups of the lipids. These polar interactions can be disrupted by adding salts or by changing the pH. Many peripheral membrane proteins are bound to the surface of integral proteins on either the cytoplasmic or the extracellular side of the membrane.
Secondary Structure of Membrane Proteins Proteins can span the membrane with alpha helices. The archaeal protein bacteriorhodopsin is built almost entirely of alpha helices; seven closely packed alpha helices arranged almost perpendicularly to the plane of the cell membrane, spanning its width. Examination of the primary structure of this protein reveals that most of the amino acid residues in the alpha helices are nonpolar and only a few are charged. This distribution of nonpolar amino acids is sensible because these residues are either in contact with the hydrocarbon core of the membrane or with one another. Membrane spanning alpha helices are the most common structural motif in membrane proteins. These regions can be identified with the primary sequence alone.

## References

* ↑ Viadiu, Hector. "Membrane Properties." UCSD Lecture. November 2011.
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