Plasma Membrane

The cell membrane (also known as the plasma membrane (PM) or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of all cells from the outside environment (the extracellular space). The cell membrane consists of a lipid bilayer, made up of two layers of phospholipids with cholesterols (a lipid component) interspersed between them, maintaining appropriate membrane fluidity at various temperatures. The membrane also contains membrane proteins, including integral proteins that span the membrane and serve as membrane transporters, and peripheral proteins that loosely attach to the outer (peripheral) side of the cell membrane, acting as enzymes to facilitate interaction with the cell's environment. Glycolipids embedded in the outer lipid layer serve a similar purpose. The cell membrane controls the movement of substances in and out of cells and organelles, being selectively permeable to ions and organic molecules. In addition, cell membranes are involved in a variety of cellular processes such as cell adhesion, ion conductivity, and cell signalling and serve as the attachment surface for several extracellular structures, including the cell wall and the carbohydrate layer called the glycocalyx, as well as the intracellular network of protein fibers called the cytoskeleton. In the field of synthetic biology, cell membranes can be artificially reassembled.

History

While Robert Hooke’s discovery of cells in 1665 led to the proposal of the Cell Theory, Hooke misled the cell membrane theory that all cells contained a hard cell wall since only plant cells could be observed at the time. Microscopists focused on the cell wall for well over 150 years until advances in microscopy were made. In the early 19th century, cells were recognized as being separate entities, unconnected, and bound by individual cell walls after it was found that plant cells could be separated. This theory extended to include animal cells to suggest a universal mechanism for cell protection and development. By the second half of the 19th century, microscopy was still not advanced enough to make a distinction between cell membranes and cell walls. However, some microscopists correctly identified at this time that while invisible, it could be inferred that cell membranes existed in animal cells due to intracellular movement of components internally but not externally and that membranes were not the equivalent of a cell wall to a plant cell. It was also inferred that cell membranes were not vital components to all cells. Many refuted the existence of a cell membrane still towards the end of the 19th century. In 1890, an update to the Cell Theory stated that cell membranes existed, but were merely secondary structures. It was not until later studies with osmosis and permeability that cell membranes gained more recognition. In 1895, Ernest Overton proposed that cell membranes were made of lipids.

The lipid bilayer hypothesis, proposed in 1925 by Gorter and Grendel, created speculation in the description of the cell membrane bilayer structure based on crystallographic studies and soap bubble observations. In an attempt to accept or reject the hypothesis, researchers measured membrane thickness. These researchers extracted the lipid from human red blood cells and measured the amount of surface area the lipid would cover when spread over the surface of the water. Since mature mammalian red blood cells lack both nuclei and cytoplasmic organelles, the plasma membrane is the only lipid-containing structure in the cell. Consequently, all of the lipids extracted from the cells can be assumed to have resided in the cells’ plasma membranes. The ratio of the surface area of water covered by the extracted lipid to the surface area calculated for the red blood cells from which the lipid was 2:1(approx) and they concluded that the plasma membrane contains a lipid bilayer.

In 1925 it was determined by Fricke that the thickness of erythrocyte and yeast cell membranes ranged between 3.3 and 4 nm, a thickness compatible with a lipid monolayer. The choice of the dielectric constant used in these studies was called into question but future tests could not disprove the results of the initial experiment. Independently, the leptoscope was invented in order to measure very thin membranes by comparing the intensity of light reflected from a sample to the intensity of a membrane standard of known thickness. The instrument could resolve thicknesses that depended on pH measurements and the presence of membrane proteins that ranged from 8.6 to 23.2 nm, with the lower measurements supporting the lipid bilayer hypothesis. Later in the 1930s, the membrane structure model developed in general agreement to be the paucimolecular model of Davson and Danielli (1935). This model was based on studies of surface tension between oils and echinoderm eggs. Since the surface tension values appeared to be much lower than would be expected for an oil–water interface, it was assumed that some substance was responsible for lowering the interfacial tensions in the surface of cells. It was suggested that a lipid bilayer was in between two thin protein layers. The paucimolecular model immediately became popular and it dominated cell membrane studies for the following 30 years, until it became rivaled by the fluid mosaic model of Singer and Nicolson (1972).S J Singer and G L Nicolson."The fluid mosaic model of the structure of cell membranes." Science. (1972) 175. 720-731.

Despite the numerous models of the cell membrane proposed prior to the fluid mosaic model, it remains the primary archetype for the cell membrane long after its inception in the 1970s. Although the fluid mosaic model has been modernized to detail contemporary discoveries, the basics have remained constant: the membrane is a lipid bilayer composed of hydrophilic exterior heads and a hydrophobic interior where proteins can interact with hydrophilic heads through polar interactions, but proteins that span the bilayer fully or partially have hydrophobic amino acids that interact with the non-polar lipid interior. The fluid mosaic model not only provided an accurate representation of membrane mechanics, it enhanced the study of hydrophobic forces, which would later develop into an essential descriptive limitation to describe biological macromolecules.

For many centuries, the scientists cited disagreed with the significance of the structure they were seeing as the cell membrane. For almost two centuries, the membranes were seen but mostly disregarded as an important structure with cellular function. It was not until the 20th century that the significance of the cell membrane as it was acknowledged. Finally, two scientists Gorter and Grendel (1925) made the discovery that the membrane is “lipid-based”. From this, they furthered the idea that this structure would have to be in a formation that mimicked layers. Once studied further, it was found by comparing the sum of the cell surfaces and the surfaces of the lipids, a 2:1 ratio was estimated; thus, providing the first basis of the bilayer structure known today. This discovery initiated many new studies that arose globally within various fields of scientific studies, confirming that the structure and functions of the cell membrane are widely accepted.

The structure has been variously referred to by different writers as the ectoplast ( de Vries, 1885), ''Plasmahaut'' (plasma skin, Pfeffer, 1877, 1891), ''Hautschicht'' (skin layer, Pfeffer, 1886; used with a different meaning by Hofmeister, 1867), plasmatic membrane (Pfeffer, 1900), plasma membrane, cytoplasmic membrane, cell envelope and cell membrane. Some authors who did not believe that there was a functional permeable boundary at the surface of the cell preferred to use the term plasmalemma (coined by Mast, 1924) for the external region of the cell.

Composition

Cell membranes contain a variety of biological molecules, notably lipids and proteins. Composition is not set, but constantly changing for fluidity and changes in the environment, even fluctuating during different stages of cell development. Specifically, the amount of cholesterol in human primary neuron cell membrane changes, and this change in composition affects fluidity throughout development stages.

Material is incorporated into the membrane, or deleted from it, by a variety of mechanisms:
* Fusion of intracellular vesicles with the membrane (exocytosis) not only excretes the contents of the vesicle but also incorporates the vesicle membrane's components into the cell membrane. The membrane may form blebs around extracellular material that pinch off to become vesicles (endocytosis).
* If a membrane is continuous with a tubular structure made of membrane material, then material from the tube can be drawn into the membrane continuously.
* Although the concentration of membrane components in the aqueous phase is low (stable membrane components have low solubility in water), there is an exchange of molecules between the lipid and aqueous phases.

Lipids

The cell membrane consists of three classes of amphipathic lipids: phospholipids, glycolipids, and sterols. The amount of each depends upon the type of cell, but in the majority of cases phospholipids are the most abundant, often contributing for over 50% of all lipids in plasma membranes. Glycolipids only account for a minute amount of about 2% and sterols make up the rest. In red blood cell studies, 30% of the plasma membrane is lipid. However, for the majority of eukaryotic cells, the composition of plasma membranes is about half lipids and half proteins by weight.

The fatty chains in phospholipids and glycolipids usually contain an even number of carbon atoms, typically between 16 and 20. The 16- and 18-carbon fatty acids are the most common. Fatty acids may be saturated or unsaturated, with the configuration of the double bonds nearly always "cis". The length and the degree of unsaturation of fatty acid chains have a profound effect on membrane fluidity as unsaturated lipids create a kink, preventing the fatty acids from packing together as tightly, thus decreasing the melting temperature (increasing the fluidity) of the membrane. The ability of some organisms to regulate the fluidity of their cell membranes by altering lipid composition is called homeoviscous adaptation.

The entire membrane is held together via non-covalent interaction of hydrophobic tails, however the structure is quite fluid and not fixed rigidly in place. Under physiological conditions phospholipid molecules in the cell membrane are in the liquid crystalline state. It means the lipid molecules are free to diffuse and exhibit rapid lateral diffusion along the layer in which they are present. However, the exchange of phospholipid molecules between intracellular and extracellular leaflets of the bilayer is a very slow process. Lipid rafts and caveolae are examples of cholesterol-enriched microdomains in the cell membrane. Also, a fraction of the lipid in direct contact with integral membrane proteins, which is tightly bound to the protein surface is called annular lipid shell; it behaves as a part of protein complex.

In animal cells cholesterol is normally found dispersed in varying degrees throughout cell membranes, in the irregular spaces between the hydrophobic tails of the membrane lipids, where it confers a stiffening and strengthening effect on the membrane. Additionally, the amount of cholesterol in biological membranes varies between organisms, cell types, and even in individual cells. Cholesterol, a major component of animal plasma membranes, regulates the fluidity of the overall membrane, meaning that cholesterol controls the amount of movement of the various cell membrane components based on its concentrations. In high temperatures, cholesterol inhibits the movement of phospholipid fatty acid chains, causing a reduced permeability to small molecules and reduced membrane fluidity. The opposite is true for the role of cholesterol in cooler temperatures. Cholesterol production, and thus concentration, is up-regulated (increased) in response to cold temperature. At cold temperatures, cholesterol interferes with fatty acid chain interactions. Acting as antifreeze, cholesterol maintains the fluidity of the membrane. Cholesterol is more abundant in cold-weather animals than warm-weather animals. In plants, which lack cholesterol, related compounds called sterols perform the same function as cholesterol.

Phospholipids forming lipid vesicles

Lipid vesicles or liposomes are approximately spherical pockets that are enclosed by a lipid bilayer. These structures are used in laboratories to study the effects of chemicals in cells by delivering these chemicals directly to the cell, as well as getting more insight into cell membrane permeability. Lipid vesicles and liposomes are formed by first suspending a lipid in an aqueous solution then agitating the mixture through sonication, resulting in a vesicle. By measuring the rate of efflux from that of the inside of the vesicle to the ambient solution, allows researcher to better understand membrane permeability. Vesicles can be formed with molecules and ions inside the vesicle by forming the vesicle with the desired molecule or ion present in the solution. Proteins can also be embedded into the membrane through solubilizing the desired proteins in the presence of detergents and attaching them to the phospholipids in which the liposome is formed. These provide researchers with a tool to examine various membrane protein functions.

Carbohydrates

Plasma membranes also contain carbohydrates, predominantly glycoproteins, but with some glycolipids ( cerebrosides and gangliosides). Carbohydrates are important in the role of cell-cell recognition in eukaryotes; they are located on the surface of the cell where they recognize host cells and share information, viruses that bind to cells using these receptors cause an infection For the most part, no glycosylation occurs on membranes within the cell; rather generally glycosylation occurs on the extracellular surface of the plasma membrane. The glycocalyx is an important feature in all cells, especially epithelia with microvilli. Recent data suggest the glycocalyx participates in cell adhesion, lymphocyte homing, and many others. The penultimate sugar is galactose and the terminal sugar is sialic acid, as the sugar backbone is modified in the Golgi apparatus. Sialic acid carries a negative charge, providing an external barrier to charged particles.

Proteins

The cell membrane has large content of proteins, typically around 50% of membrane volume These proteins are important for the cell because they are responsible for various biological activities. Approximately a third of the genes in yeast code specifically for them, and this number is even higher in multicellular organisms. Membrane proteins consist of three main types: integral proteins, peripheral proteins, and lipid-anchored proteins.

As shown in the adjacent table, integral proteins are amphipathic transmembrane proteins. Examples of integral proteins include ion channels, proton pumps, and g-protein coupled receptors. Ion channels allow inorganic ions such as sodium, potassium, calcium, or chlorine to diffuse down their electrochemical gradient across the lipid bilayer through hydrophilic pores across the membrane. The electrical behavior of cells (i.e. nerve cells) are controlled by ion channels. Proton pumps are protein pumps that are embedded in the lipid bilayer that allow protons to travel through the membrane by transferring from one amino acid side chain to another. Processes such as electron transport and generating ATP use proton pumps. A G-protein coupled receptor is a single polypeptide chain that crosses the lipid bilayer seven times responding to signal molecules (i.e. hormones and neurotransmitters). G-protein coupled receptors are used in processes such as cell to cell signaling, the regulation of the production of cAMP, and the regulation of ion channels.

The cell membrane, being exposed to the outside environment, is an important site of cell–cell communication. As such, a large variety of protein receptors and identification proteins, such as antigens, are present on the surface of the membrane. Functions of membrane proteins can also include cell–cell contact, surface recognition, cytoskeleton contact, signaling, enzymatic activity, or transporting substances across the membrane.

Most membrane proteins must be inserted in some way into the membrane. For this to occur, an N-terminus "signal sequence" of amino acids directs proteins to the endoplasmic reticulum, which inserts the proteins into a lipid bilayer. Once inserted, the proteins are then transported to their final destination in vesicles, where the vesicle fuses with the target membrane.

Function

The cell membrane surrounds the cytoplasm of living cells, physically separating the intracellular components from the extracellular environment. The cell membrane also plays a role in anchoring the cytoskeleton to provide shape to the cell, and in attaching to the extracellular matrix and other cells to hold them together to form tissues. Fungi, bacteria, most archaea, and plants also have a cell wall, which provides a mechanical support to the cell and precludes the passage of larger molecules.

The cell membrane is selectively permeable and able to regulate what enters and exits the cell, thus facilitating the transport of materials needed for survival. The movement of substances across the membrane can be achieved by either passive transport, occurring without the input of cellular energy, or by active transport, requiring the cell to expend energy in transporting it. The membrane also maintains the cell potential. The cell membrane thus works as a selective filter that allows only certain things to come inside or go outside the cell. The cell employs a number of transport mechanisms that involve biological membranes:

1. Passive osmosis and diffusion: Some substances (small molecules, ions) such as carbon dioxide (CO₂) and oxygen (O₂), can move across the plasma membrane by diffusion, which is a passive transport process. Because the membrane acts as a barrier for certain molecules and ions, they can occur in different concentrations on the two sides of the membrane. Diffusion occurs when small molecules and ions move freely from high concentration to low concentration in order to equilibrate the membrane. It is considered a passive transport process because it does not require energy and is propelled by the concentration gradient created by each side of the membrane. Such a concentration gradient across a semipermeable membrane sets up an osmotic flow for the water. Osmosis, in biological systems involves a solvent, moving through a semipermeable membrane similarly to passive diffusion as the solvent still moves with the concentration gradient and requires no energy. While water is the most common solvent in cell, it can also be other liquids as well as supercritical liquids and gases.

2. Transmembrane protein channels and