Biochemistry/Lipids And The Plasma Membrane

Membranes And Lipids
All cells, from simple prokaryotic bacteria to complex multicellular organisms are surrounded by a membrane. The membrane acts as a selective barrier, letting some substances into the cell and preventing other substances from entering,and it also actively transports substances between the inside and outside of the cell, using cellular energy to do so. This is important in regulating the concentration of many substances which must be maintained within strict limits. The cell also contains membrane bound compartments, where the membrane acts as a barrier for the separation of different environments, like lysosomes which have a high pH that would be toxic to the rest of the cell. Furthermore, lipids are polar molecules that are generally soluble in organic solvents due to large number of nonpolar bonds in lipids. Their ability to form membranes are as a result of their hydrophobic properties, which is contributed by their fatty acids. Membranes are amphipatic.

The Lipid Bilayer
The first person to link lipids with the cell membrane may have been Charles Ernest Overton, who was studying heredity in plants. Part of his studies involved studying which substances absorbed into plant cells most quickly. After characterizing a large number of substances, he came up with the idea that cell membranes were composed of something similar to the lipids found in vegetable oils, and that substances are absorbed into the cells by dissolving through the membrane.

The next big step came when Gorter and Grendel extracted the lipids from red blood cells and compared the surface area of the lipids spread out on water compared to the surface area of the red blood cells. They found the lipid surface area was twice that of the red blood cells, and concluded that the lipids must be arranged in a layer two lipid molecules thick. Lipid bilayer is a double layer membrane formed from phospholipids. Phospholipids are composed of a polar head group and non-polar fatty acid tails. The arrangement of the phospholipids makes the cell membrane permeable.

Fatty Acids
A fatty acid is a linear of carboxylic acid with a long hydrocarbon chain. In fatty acids, the non-polar hydrocarbon chain gives the molecule a non- polar character Fatty acids usually have between 14 and 24 carbon atoms and their carbon chain may have one or more double bonds. In naturally occurring fatty acids, these double bonds are mostly in cis configuration. Fatty acids have both common names and systematic names. The systematic name is based on the alkane or alkene with the same number of carbon atoms, with the final e of the hydrocarbon replaced with oic acid, if the carbon chain of the fatty acid is saturated (without double bond in its carbon chain), and "enoic acid" if there is double in its carbon chain. For example Laurate (Figure x) is a fatty acid with 12 carbon atoms and no double bonds, so the systematic name is dodecanoic acid, and the ionized form is dodecanoate. (saturated fatty acid table) If there are double bonds, the location is marked with the symbol Δ with a superscript number indicating the location of the double bond and preceded by cis or trans to indicate configuration (but almost invariably cis). Carbon atoms are counted from the carboxyl end, as in Figure x, so a dodecenoate acid with a cis double bond between carbon atoms 9 and 10 would be: cis-Δ9-dodecenoate.

The number 2, 3 and last carbon atom are called the α, β and ω atoms, respectively.

Biological fatty acids usually contain an even number of carbon atoms, with numbers of 16 and 18 being most common. The length of the fatty acid chain and the degree of saturation contributes largely to their distinct properties. The shorter the chain length and the more unsaturation in the fatty acid enhances their fluidity, thus lowering their melting point.

Phosphoglycerides
Phosphoglycerides are esters of two fatty acids, phosphoric acid and a trifunctional alcohol- glycerol. The fatty acids are attached to the glycerol at the 1 and 2 positions on glycerol through ester bonds. Phosphoglycerides are composed of a glycerol back bone with substituents in the following arrangements: The simplest phosphoglyceride is phosphatidate (picture). Other phosphoglycerides can be made when a group with a hydroxyl is esterified to the phosphate group of phosphatidate. There are four common substituents for phosphatidate. Serine, ethanolamine and choline are structurally similar, while inositol is different:
 * Hydroxyl #1 of glycerol is usually esterified to a saturated fatty acid
 * Hydroxyl #2 of glycerol is usually esterified to an unsaturated fatty acid
 * Hydroxyl #3 of glycerol is esterified to a phosphate group

Sphingolipids
Sphingolipids are a second type of lipid found in cell membranes, particularly nerve cells and brain tissues. They do not contain glycerol, but retain the two alcohols with the middle position occupied by an amine and have the same overall shape as phosphoglycerides but have different chemistry, using sphingosine in place of glycerol. Sphingosine has a long hydrocarbon tail similar to fatty acids attached to a structure that is similar to the amino acid serine. A fatty acid can attach to the amine group, and a "head" group can attach to a hydroxyl (see Figure x). Sphingolipids are named according to this head group:
 * If there is no head group it is called a ceramide
 * If the head group is phosphate and choline, it is called sphingomyelin
 * If the head group is a sugar, it is called a glycosphingolipid (or a glycolipid)

The majority of sphingolipids are of the third type, glycosphingolipids. It is thought they have functions in cell recognition and protection in addition to their structural role in the membrane.

Formation Of The Bilayer
If we compare the structures of phosphoglycerides and sphingolipids, we see that they are very similar compounds. Each lipid has two long hydrophobic hydrocarbon "tails" and a single polar "head". Since the molecule has both polar and nonpolar moieties, it is said to be amphipathic. It is the amphipathic nature of these molecules that causes them to form bilayers, mediated by four forces:
 * The hydrophobic effect- this causes the hydrophobic tails to come together. This is the strongest force driving the formation of the bilayer. It is a consequence of the increased entropy in water molecules when non polar substances are aggregated in water.
 * Van der Walls forces between the hydrophobic tails.
 * Electrostatic forces of the head groups.
 * Hydrogen bonds between the head groups.

One possible structure that satisfies the above forces is called a micelle (pictures). This is common with free fatty acids, but not with most phosphoglycerides and sphingolipids because these groups have twice as many acyl chains per head than the fatty acid (picture), and it is difficult to pack them all into the center of the micelle. Phospholipids and sphingolipids more often form a bilayer in a sheet or a sphere (picture). This is the so called lipid bilayer. Lipid bilayer is permeable to water molecules and other small, uncharged molecules like oxygen, carbon dioxide. A bimolecular sheet formed by amphipathic molecules in which the hydrophobic moieties are on the inside of the sheet and the hydrophilic ones are on the aqueous outside.

Studying Motion
NMR, ESR, X-Ray, Differential scanning calorimetry

Intramolecular Motion
There are three basic kinds of motion within the lipid molecules: stretching between bonds, rotating between bonds, and wagging between bonds (?). [picture] 99% of motion within liquid crystal is due to rotation about carbon-carbon bonds. Unsaturated fatty acids of membrane lipids rotate more often. This is because of the packed arrangement of the lipid bilayer. When there is rotation about one bond, an adjacent bond rotates to compensate for steric clashes [pictures]. Since double bonds in fatty acids are nearly always cis, they introduce kinks in the fatty acid. When a bond adjacent to a double bond rotates, the other bond adjacent to the double bond also rotates, and the whole thing moves like an old fashioned bit and brace [pictures]. It takes more energy to rotate the double bonds closer to the head groups due to [angle thing picture]. Double bonds react with O2 readily and create poisons [more] bacteria have [cyclopropane picture]. Furthermore, NMR rotating frame relaxation studies of the intramolecular motion in methionine-enkephalin.

Diffusion
One of the most notable properties of the lipid membrane is the ability of a single lipid to diffuse. This property was discovered using the "fluorescence recovery after photobleaching," also known as FRAP. In this experiment, the cell surface is first labeled with a fluorescent chromophore. Afterwards, a specific region is then bleached with intense light, leaving a prominent mark. In the bleached area, the experimenters noticed that as time progressed, bleached molecules moved out from the bleached area and unbleached molecules moved towards the bleached area. This shows that the lipid bilayer allows for molecule movement within the membrane.

There are two kinds of diffusion: lateral and transverse (flip-flop). The lateral diffusion is exactly as it sounds like. In a lipid bilayer, one lipid molecule can move pass the adjacent one. The transverse molecule works a bit differently. It still displaces one over its adjacent counterpart, and crosses over to the other side of the lipid bilayer. It is important to note that the lateral diffusion is substantially faster than the transverse. Studies show that the transverse diffusion only happens once every few hours. Diffusion is the movement of a particle from area of high concentration to low concentration, and it is not to be confused with osmosis, which is the movement of water through a semi-permeable membrane. Diffusion depends on CO2 and O2 concentrate inside and outside of alveolar sack.

Transportation Methods
The membrane regulates molecule transport through a variety of means. There are two general categories that each transportation regulation falls into: passive transport and active transport. Passive transport is the movement of molecules down its concentration gradient: in other words, higher concentration to lower concentration. The diffusion of water, a special case, is called "osmosis." Not all molecules can diffuse through the phospholipid bilayer. The ones that can are usually hydrophobic molecules (i.e. oxygen), nonpolar molecules (i.e. benzene), or small uncharged polar molecules (i.e. water). The hydrophobic and nonpolar molecules can dissolve through the bilayer because of the similar polarites of the bilayer and the molecule itself. The small uncharged polar molecules usually require a membrane channel to diffuse i.e. aquaporins for water. The molecules that do not pass through the layer with ease are large & uncharged, polar, or ions. Examples of each are glucose, sucrose, and hydrogen ion, respectively. To sum up the defining characteristics of what passes or does not pass through the membrane, they are size, charge, and polarity.

Normally, hydrophilic molecules would not be able to cross the phospholipid bilayer due to the difference in polarities. However, it is observed that hydrophilic molecules do cross the membrane protein through a different mechanism than the hydrophobic molecules. While hydrophobic molecules diffuse through the membrane due to their similar polarities, hydrophilic molecules require a molecule called a membrane protein (integral or peripheral), which transfers the molecule in both active and passive transport. A few examples of passive transport are simple diffusion and facilitated diffusion. Simple diffusion is when a solute moves from an area of high concentration to an area of low concentration to establish equilibrium via a channel protein. Facilitated diffusion still moves from an area of higher concentration to lower concentration but instead of a channel protein, it is a carrier protein. This carrier protein, also called permeases, accelerates the rate of transport greatly. Active transport moves the molecules from an area of low concentration to an area of high concentration (the opposite of passive transport). This transport moving molecules up its concentration gradient requires energy, usually from ATP (adenosine triphosphate). A common example used to explain this concept is the sodium-potassium pump. In the human cell, there is usually a high concentration of sodium on the outside the cell and a low concentration of sodium inside the cell. The opposite applies to the concentrations of potassium: high on the inside and low on the outside. The mechanism begins by sodium ion binding to the sodium-potassium pump protein with its gap close off from the cell's external environment. The binding of sodium ion signals to the cell to use convert ATP to ADP (adenosine triphosphate). This reaction will release energy and add a phosphate group to the protein, enabling the protein to change its conformation and release the bound sodium ions to the external cell environment. After the release of sodium ions, potassium ions from the same area will bind to the protein. The potassium ion binding will signal to the protein to convert the bound phosphate group to unbound inorganic phosphate and change the conformation of the protein to release the potassium ions into the cell. Afterwards, the sodium ions bind again and the cycle repeats.

A few other energy-driven processes are endocytosis and exocytosis. Endocytosis are when large molecules are transported into the cell. Exocytosis are when molecules are expelled from the cell. An example of receptor-mediated endocytosis occurs in eukaryotes. It is important for the different membranes in the cell to either join or separate in order to perform certain functions such as engulf, transport, or even release molecules essential for the body. This process is facilitated by LDL, a low-density lipoprotein. External cellular LDL float first binds to its corresponding receptor, called the LDL receptor. The cell membrane then engulfs the LDL and the LDL receptor into the cell, forming a vesicle to keep it unharmed from the cell hydrophilic environment. The complex then separates to protein and receptor counterparts. The LDL fuses with a lysosome, breaking down the LDL with the release of cholesterol as a by-product. A short example of exocytosis would be either the insulin secretion in the blood, or the transport of neurotransmitters at the gap junction during an action potential. A more specific example lies in Golgi's vesicular transport. In eukaryotes, the endoplasmic reticulum (ER) sends transport vesicles to the Golgi apparatus created from proteins. Some of the vesicles fuse with the lysosomes resulting in digestion. Some of the other transport vesicles with essential proteins for the plasma membrane will diffuse in to the membrane due to their similar polarities, releasing the protein content out into the cell's environment.

Different concentrations with regards to internal and external cell environment have different effects on animal cells and plant cells. In a hypertonic solution (concentration of solute is greater on the outside than on the inside), the cell would attempt to create an equilibrium by releasing its water content to the external cell environment. By doing so, the concentrations may be equal if there is enough water in the cell. Also, the cell would end up being shriveled. In the plant cell, the same things occurs. However, because plant cells have cell walls, instead of being shriveled, it is plasmolyzed. On the other extreme, hypotonic solution, when the concentration is solute is lower on the outside than the inside, the cell will become lysed. The attempt to establish equilibrium lies in the water's entrance into the cell to lower the concentration in the cell. In the plant cell, this is called turgid instead of lysed. On a sidenote, this is the normal preference of the plant cell. In an isotonic solution (concentrations are equal on both sides of the cell), the net content of water in and out of the cell remains the cell. This is the eukaryote's preferred state. In the plant cell, it is termed flaccid. Membrance proteins called transporters facilitate the passage of molecules across membrance, there is involved at least three step: dinding, conformational change fo the protein, and release. There are two types of transporter: passive transporters which use no energy, and active transporters that employ ATP to drive transport.

Cell Communication
cell-to- cell communication is essential for multicellular organisms such as human or an oak creatures in which they must communicate in order for them to develop from fertilized egg and then survive and reproduce in turn. Communication between cells is very important for many unicellular organisms that must find matters and food in order for them to develop and to sexually reproduce. An early example of cell communication is Saccharomyces cerevisiae in which the cells of that yeast use chemical signaling to identify cells of opposite mating and to start the mating process. The study of cell communication could help to answer some of the most important questions and medicine in areas ranging between embryological development to hormone action to the development of cancer and other related diseases.

On a side note, not only is cell-to-cell communication imperative, but also with other molecules. Different kinds of molecules communicate differently with the internal programming of the cell. For example, synaptic transmitters, such as acetylcholine, bind to a certain G-protein and activates intracellular 2nd messengers. Another way for synaptic transmitters to bind is via a protein complex (integral/membrane protein) including an ion channel. The net result of both pathways change the state of ion channel conformation in the membrane. Another example, steroid hormones, diffuse through the cell membrane and eventually changes the protein programming in certain cells. As for the peptide hormone, it binds to a G-protein, activates intracellular 2nd messengers, and changes the transcription paradigm. Due to the peptide hormone's hydrophobic character and the cell membrane nonpolarity, it requires secondary messenger interaction whereas the steroid hormone (also nonpolar) can directly communicate and diffuse into the cell. Cell-cell communication is essential for multicellular organisms. Cells usually communicate by releasing chemical messenger targeted for cell. Some messengers travel short distances such as molecules are allied local regulators. Animal growth factors which are compounds that stimulate nearby target cells to grow and multiply. Numerous cells can simulaneously receive and respond to the molecules of growth factors produced by single cell in their vicinity.

Cell Adhesion
Cell adhesion is any glandular cells in ctenophores, turbellarian used for adhesion to a substrate and for capture. Cell adhesion occurs when one cell binds to another surface such as another cell or some other inanimate surface. Cell adhesion molecules serve as intermediates that hold the cell to another surface.