Cell membrane

Robert Hooke's discovery of cells in 1665 led to the proposal of the cell theory. Initially it was believed that all cells contained a hard cell wall since only plant cells could be observed at the time. 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). 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 (PtdCho), phosphatidylethanolamine (PtdEtn), phosphatidylinositol (PtdIns), phosphatidylserine (PtdSer).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. 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. Measuring the rate of efflux from the inside of the vesicle to the ambient solution allows researchers 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, 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. 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: • 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. • Transmembrane protein channels and transporters: Transmembrane proteins extend through the lipid bilayer of the membranes; they function on both sides of the membrane to transport molecules across it. Nutrients, such as sugars or amino acids, must enter the cell, and certain products of metabolism must leave the cell. Such molecules can diffuse passively through protein channels such as aquaporins in facilitated diffusion or are pumped across the membrane by transmembrane transporters. Protein channel proteins, also called permeases, are usually quite specific, and they only recognize and transport a limited variety of chemical substances, often limited to a single substance. Another example of a transmembrane protein is a cell-surface receptor, which allow cell signaling molecules to communicate between cells. The deformation then pinches off from the membrane on the inside of the cell, creating a vesicle containing the captured substance. Endocytosis is a pathway for internalizing solid particles ("cell eating" or phagocytosis), small molecules and ions ("cell drinking" or pinocytosis), and macromolecules. Endocytosis requires energy and is thus a form of active transport. • Exocytosis: Just as material can be brought into the cell by invagination and formation of a vesicle, the membrane of a vesicle can be fused with the plasma membrane, extruding its contents to the surrounding medium. This is the process of exocytosis. Exocytosis occurs in various cells to remove undigested residues of substances brought in by endocytosis, to secrete substances such as hormones and enzymes, and to transport a substance completely across a cellular barrier. In the process of exocytosis, the undigested waste-containing food vacuole or the secretory vesicle budded from Golgi apparatus, is first moved by cytoskeleton from the interior of the cell to the surface. The vesicle membrane comes in contact with the plasma membrane. The lipid molecules of the two bilayers rearrange themselves and the two membranes are, thus, fused. A passage is formed in the fused membrane and the vesicles discharges its contents outside the cell. == Prokaryotes ==

Prokaryotes are divided into two different groups: Archaea and Bacteria, with bacteria dividing further into gram-positive and gram-negative. Gram-negative bacteria have both a plasma membrane and an outer membrane separated by periplasm; however, other prokaryotes have only a plasma membrane. These two membranes differ in many aspects. The outer membrane of the gram-negative bacteria differs from other prokaryotes due to lipopolysaccharides forming the exterior of the bilayer, and lipoproteins and phospholipids forming the interior. The outer membrane typically has a porous quality due to membrane proteins such as porins, which are pore-forming proteins. The inner plasma membrane is also generally symmetric, whereas the outer membrane is asymmetric because of proteins such as the aforementioned. Also, for the prokaryotic membranes, there are multiple things that can affect the fluidity. One of the major factors that can affect the fluidity is fatty acid composition. For example, when Staphylococcus aureus was grown at 37 °C for 24 h, the membrane exhibited a more fluid state instead of a gel-like state. This supports the concept that in higher temperatures, the membrane is more fluid than in colder temperatures. When the membrane is becoming more fluid and needs to become more stabilized, it will make longer fatty acid chains or saturated fatty acid chains in order to help stabilize the membrane. Bacteria are also surrounded by a cell wall composed of peptidoglycan (amino acids and sugars). Some eukaryotic cells also have cell walls, but none that are made of peptidoglycan. The outer membrane of gram negative bacteria is rich in lipopolysaccharides, which are combined poly- or oligosaccharide and saccharolipid that stimulate the cell's natural immunity. The outer membrane can bleb out into periplasmic protrusions under stress conditions or upon virulence requirements while encountering a host target cell, and thus such blebs may work as virulence organelles. Bacterial cells provide numerous examples of the diverse ways in which prokaryotic cell membranes are adapted with structures that suit the organism's niche. For example, proteins on the surface of certain bacterial cells aid in their gliding motion. Many gram-negative bacteria have cell membranes which contain ATP-driven protein exporting systems. == Structures ==

Fluid mosaic model According to the fluid mosaic model of S. J. Singer and G. L. Nicolson (1972), which replaced the earlier model of Davson and Danielli, biological membranes can be considered as a two-dimensional liquid in which lipid and protein molecules diffuse more or less easily. Although the lipid bilayers that form the basis of the membranes do indeed form two-dimensional liquids by themselves, the plasma membrane also contains a large quantity of proteins, which provide more structure. Examples of such structures are protein-protein complexes, pickets and fences formed by the actin-based cytoskeleton, and potentially lipid rafts. Lipid bilayer . The yellow polar head groups separate the grey hydrophobic tails from the aqueous cytosolic and extracellular environments. Lipid bilayers form through the process of self-assembly. The cell membrane consists primarily of a thin layer of amphipathic phospholipids that spontaneously arrange so that the hydrophobic "tail" regions are isolated from the surrounding water while the hydrophilic "head" regions interact with the intracellular (cytosolic) and extracellular faces of the resulting bilayer. This forms a continuous, spherical lipid bilayer. Hydrophobic interactions (also known as the hydrophobic effect) are the major driving forces in the formation of lipid bilayers. An increase in interactions between hydrophobic molecules (causing clustering of hydrophobic regions) allows water molecules to bond more freely with each other, increasing the entropy of the system. This complex interaction can include noncovalent interactions such as van der Waals, electrostatic and hydrogen bonds. Lipid bilayers are generally impermeable to ions and polar molecules. The arrangement of hydrophilic heads and hydrophobic tails of the lipid bilayer prevent polar solutes (ex. amino acids, nucleic acids, carbohydrates, proteins, and ions) from diffusing across the membrane, but generally allows for the passive diffusion of hydrophobic molecules. This affords the cell the ability to control the movement of these substances via transmembrane protein complexes such as pores, channels and gates. Flippases and scramblases concentrate phosphatidyl serine, which carries a negative charge, on the inner membrane. Along with NANA, this creates an extra barrier to charged moieties moving through the membrane. Membranes serve diverse functions in eukaryotic and prokaryotic cells. One important role is to regulate the movement of materials into and out of cells. The phospholipid bilayer structure (fluid mosaic model) with specific membrane proteins accounts for the selective permeability of the membrane and passive and active transport mechanisms. In addition, membranes in prokaryotes and in the mitochondria and chloroplasts of eukaryotes facilitate the synthesis of ATP through chemiosmosis. It faces outwards, towards the interstitium, and away from the lumen. Basolateral membrane is a compound phrase referring to the terms "basal (base) membrane" and "lateral (side) membrane", which, especially in epithelial cells, are identical in composition and activity. Proteins (such as ion channels and pumps) are free to move from the basal to the lateral surface of the cell or vice versa in accordance with the fluid mosaic model. Tight junctions join epithelial cells near their apical surface to prevent the migration of proteins from the basolateral membrane to the apical membrane. The basal and lateral surfaces thus remain roughly equivalent to one another, yet distinct from the apical surface. Membrane structures The cell membrane can form different types of "supramembrane" structures such as caveolae, postsynaptic densities, podosomes, invadopodia, focal adhesions, and different types of cell junction. These structures are usually responsible for cell adhesion, communication, endocytosis and exocytosis. They are composed of specific proteins, such as integrins and cadherins. They can be visualized by electron microscopy or fluorescence microscopy. Cytoskeleton The cytoskeleton is found underlying the cell membrane in the cytoplasm and provides a scaffolding for membrane proteins to anchor to, as well as forming organelles that extend from the cell. Indeed, cytoskeletal elements interact extensively and intimately with the cell membrane. Anchoring proteins restricts them to a particular cell surface — for example, the apical surface of epithelial cells that line the vertebrate gut — and limits how far they may diffuse within the bilayer. The cytoskeleton is able to form appendage-like organelles, such as cilia, which are microtubule-based extensions covered by the cell membrane, and filopodia, which are actin-based extensions. These extensions are ensheathed in membrane and project from the surface of the cell in order to sense the external environment and/or make contact with the substrate or other cells. The apical surfaces of epithelial cells are dense with actin-based finger-like projections known as microvilli, which increase cell surface area and thereby increase the absorption rate of nutrients. Localized decoupling of the cytoskeleton and cell membrane results in formation of a bleb. Intracellular membranes The content of the cell, inside the cell membrane, is composed of numerous membrane-bound organelles, which contribute to the overall function of the cell. The origin, structure, and function of each organelle leads to a large variation in the cell composition due to the individual uniqueness associated with each organelle. • Mitochondria and chloroplasts are considered to have evolved from bacteria, known as the endosymbiotic theory. This theory arose from the idea that Paracoccus and Rhodopseudomonas, types of bacteria, share similar functions to mitochondria and blue-green algae (cyanobacteria) share similar functions to chloroplasts. Endosymbiotic theory proposes that through the course of evolution, a eukaryotic cell engulfed these two types of bacteria, leading to the formation of mitochondria and chloroplasts inside eukaryotic cells. This engulfment lead to the double-membranes systems of these organelles in which the outer membrane originated from the host's plasma membrane and the inner membrane was the endosymbiont's plasma membrane. Considering that mitochondria and chloroplasts both contain their own DNA is further support that both of these organelles evolved from engulfed bacteria that thrived inside a eukaryotic cell. • In eukaryotic cells, the nuclear membrane separates the contents of the nucleus from the cytoplasm of the cell. The nuclear membrane is formed by an inner and outer membrane, providing the strict regulation of materials in to and out of the nucleus. Materials move between the cytosol and the nucleus through nuclear pores in the nuclear membrane. If a cell's nucleus is more active in transcription, its membrane will have more pores. The protein composition of the nucleus can vary greatly from the cytosol as many proteins are unable to cross through pores via diffusion. Within the nuclear membrane, the inner and outer membranes vary in protein composition, and only the outer membrane is continuous with the endoplasmic reticulum (ER) membrane. Like the ER, the outer membrane also possesses ribosomes responsible for producing and transporting proteins into the space between the two membranes. The nuclear membrane disassembles during the early stages of mitosis and reassembles in later stages of mitosis. • The ER, which is part of the endomembrane system, which makes up a very large portion of the cell's total membrane content. The ER is an enclosed network of tubules and sacs, and its main functions include protein synthesis, and lipid metabolism. There are 2 types of ER, smooth and rough. The rough ER has ribosomes attached to it used for protein synthesis, while the smooth ER is used more for the processing of toxins and calcium regulation in the cell. • The Golgi apparatus has two interconnected round Golgi cisternae. Compartments of the apparatus forms multiple tubular-reticular networks responsible for organization, stack connection and cargo transport that display a continuous grape-like stringed vesicles ranging from 50 to 60 nm. The apparatus consists of three main compartments, a flat disc-shaped cisterna with tubular-reticular networks and vesicles. Variations The cell membrane has different lipid and protein compositions in distinct types of cells and may have therefore specific names for certain cell types. • Sarcolemma in muscle cells: Sarcolemma is the name given to the cell membrane of muscle cells. Unlike other cell membranes, the sarcolemma makes up small channels called T-tubules that pass through the entirety of muscle cells. It has also been found that the average sarcolemma is 10 nm thick as opposed to the 4 nm thickness of a general cell membrane. • Oolemma is the cell membrane of an oocyte: The oolemma of an oocyte, (immature egg cell) is not consistent with a lipid bilayer as the bilayer is not present and does not consist of lipids. Rather, the structure has an inner layer, the fertilization envelope, and the exterior is made up of the zona pellucida (vitelline membrane in non-mammals), which is made up of glycoproteins; however, channels and proteins are still present for their functions in the membrane. • Axolemma: The specialized plasma membrane on the axons of nerve cells that is responsible for the generation of the action potential. It consists of a granular, densely packed lipid bilayer that works closely with the cytoskeleton components spectrin and actin. These cytoskeleton components are able to bind to and interact with transmembrane proteins in the axolemma. == Permeability ==

The permeability of a membrane is the rate of passive diffusion of molecules through the membrane. These molecules are known as permeant molecules. Permeability depends mainly on the electric charge and polarity of the molecule and to a lesser extent the molar mass of the molecule. Due to the cell membrane's hydrophobic nature, small electrically neutral molecules pass through the membrane more easily than charged, large ones. The inability of charged molecules to pass through the cell membrane results in pH partition of substances throughout the fluid compartments of the body. == See also ==