Cell membrane (Plasma Membrane) structures and functions

Cell membrane or Plasma Membrane

• Cell membrane (also called”the plasma membrane (PM) or the cytoplasmic membrane and has been traditionally known as”the plasmalemma) is a membrane in the body which separates the inner part and exterior of cells. It also separates them from their external environment (the extracellular spaces) and shields cells from the elements.
• The cell membrane comprises the lipid bilayer. It is composed by two layers of polyphospholipids that have cholesterols (a lipid component) interspersed between them, ensuring proper membrane fluidity at different temperatures.
• The membrane also has membrane proteins, such as integral proteins that cover the membrane and function as transporters for the membrane, as well as peripheral proteins that attach on the exterior (peripheral) part that is the membrane of cells. They are serving as enzymes that help the cell interact with its surroundings.
• Glycolipids that are embedded within the outer layer of lipid serve the same purpose.
• The cell membrane regulates the flow of chemicals into and out of organelles and cells by allowing selective permeation to organic molecules and ions.
• Cell membranes are involved in range of cell-related processes like cell adhesion cell signalling and ion conductivity and act as an connection surface for a variety of extracellular structures like the cell wall as well as the carbohydrate layer, also known as the glycocalyx, aswell being the intracellular network of protein fibers, referred to as the cytoskeleton.
• In the area of synthetic biology, cell membranes can be made artificially rebuilt.
• Lipids and proteins are the most important components of the cell’s membrane. The precise mix of lipids and proteins can differ based on the purpose of a particular cell.
• Phospholipids are essential components in cell membranes. They can spontaneously create a bilayer of lipids which is semi-permeable, meaning it is only certain compounds are able to move through the membrane and into inside the cell.
• Like the membrane of cell, certain organelles of cells are covered by membranes. The mitochondria and nucleus are two of them.

Isolation and Analysis of Plasma Membrane

• When looking through a light microscope, you won’t be able to see the plasma membrane because it’s so thin. Isolating and then artificially synthesising the plasma membrane of a variety of cells has allowed researchers to examine its structure in detail (e.g., liposome).
• Biochemical and biophysical techniques are applied to the now-isolated membranes.
• Electron microscopy, enzyme analysis, and the examination of surface antigens are all utilised to regulate the purity of isolated membranes.
• Mammalian red blood cells (erythrocytes), medullated nerve fibres, Ehrlich mouse ascites tumour cells, liver cells, striated muscle, Amoeba proteus, sea urchin eggs, and bacteria are only some of the cell types employed to examine the ultra-structure of the plasma membrane.
• However, most of what is known about plasma membrane shape and properties comes from studies of mammalian erythrocytes and the myelin sheath of nerve fibres.
• Human erythrocytes, or red blood cells, were chosen by E. Gorter and F. Grendel (1925) for this type of research because they possessed the characteristics listed below. These cells are widely accessible and are thought to be very basic. Since there are no membranes or organelles on the inside of these cells, the only membrane structure to think about is the one that covers the outside.
• In conclusion, erythrocyte plasma membranes are robust and do not easily break. The haemolysis of erythrocytes makes it simpler to remove the plasma membrane.
• Treatment with hypotonic solutions (described later in the chapter) causes cellular swelling and subsequent haemoglobin loss via endosmosis (i.e., haemolysis).
• A red cell ghost is the resultant membrane. A resealed ghost is one in which the membrane’s permeability functions have been restored after minimal haemolysis thanks to treatment.
• However, white ghost membranes result when heamolysis is more severe (i.e., the haemoglobin is completely removed) and there is no prospect of resealing.
• White ghosts can only be used for studying biochemical qualities, but resealed ghosts can be utilised for both physiological and biochemical research.
• In order to obtain plasma membrane, comparable to that of mammalian erythrocytes, the yeast, Saccharomyces cerevisiae, can have its cell wall enzymatically dissolved with the help of an enzyme from a snail’s stomach.

Components Plasma Membrane

It is made up of the following elements:

• Phospholipids: Phospholipids are the primary membrane’s material
• Peripheral proteins: Peripheral proteins are found on the inner or outer bilayer of phospholipids, but not incorporated into the hydrophobic core
• Cholesterol: Cholesterol is folded between the hydrophobic tails on the membrane of phospholipids
• Carbohydrates: Carbohydrates have been found to be linked to the proteins or lipids that are on the extracellular surface of the membrane. This leads to the creation of glycolipids and glycoproteins
• Integral proteins: Integral proteins have been discovered to be present within the bilayer of phospholipids

Structure of Cell Membrane or Plasma Membrane

Cell membranes hold a wide range in biological substances, most notably proteins and lipids.

1. Lipids

• The cell membrane is composed of three types of amphipathic lipids that include glycolipids, phospholipids and the sterols.
• The quantity of each is contingent on the kind of cell However, most of the time they are the most abundant with a majority of them accounting for more than 50% of the plasma membrane lipids.
• Glycolipids make up only a tiny amount of 22%, while the rest are sterols.
• For the vast majority of eukaryotic cells, Plasma membranes contain around half proteins and half lipids in weight.

A. Phospholipids

• The membrane bilayer is made up of numerous phospholipid molecules, each with a different sizes of heads and tails.
• These are made up of a head-molecule, the phosphate molecule Glycerol, and two chains of fatty acids.
• Head group – This is one of the polar groups e.g. the sugar or choline which means that the head end that is phospholipid hydrophilic.
• Tail of two chains of fatty acids, typically comprised of 14-24 carbons (but the most commonly used lengths of carbons range from 16 to 18). If the chain is made up of an cis double bond, the chain is kinked , which reduces the packing tightness of the membrane and expanding its motion. Because the tail is made of fat acids, it can not make hydrogen bonding with water, and thus is non-polar and non-polar.
• The molecules of phospholipids are thus amphipathic. They are both hydrophilic as well as hydrophobic.
• They create bilayers on the water, with their head group facing out , and those facing the tail group into.
• The bilayer there is van der Waal forces between the acids fatty tails of phospholipids, as well as electrostatic and hydrogen bonds between hydrophilic groups as well as water.

b. Cholesterol

• In the animal cell, cholesterol is usually found dispersed to different amounts across cell membranes. It is also found in the irregular spaces between hydrophobic tails of membrane lipids. This provides a stiffening and strengthening effect to the membrane.
• Furthermore, the quantity of cholesterol found in biological membranes is different between organisms or cell types, and even in the individual cells.
• Cholesterol is the most important component of plasma membranes in animals regulates the flow of the entire membrane. This means cholesterol regulates the quantity of movement of cells’ membrane components based upon the concentrations.
• At higher temperatures, cholesterol hinders the movement of phospholipids’ chains of fatty acids, which results in an increase in permeability for small molecules and a decrease in membrane fluidity. This is not the case regarding the function of cholesterol at lower temperatures.
• Cholesterol production, and consequently concentration, is increased (increased) as a result of cold temperatures.
• In cold temperatures cholesterol can interfere with the fatty acid chain interactions. As an antifreeze, cholesterol keeps the membrane’s fluidity.
• Cholesterol is much more abundant in warm-weather animals than cold-weather animals.
• In plants that do not have cholesterol, compounds that are related to cholesterol called Sterols serve the same purpose as cholesterol.

2. Carbohydrates

• The plasma membranes contain also carbohydrates. mostly glycoproteins. However, they also contain a few glycolipids (cerebrosides and Gangliosides).
• Carbohydrates play a crucial role of cell-cell recognition within eukaryotes. They’re located on the outside of cells where they identify host cells and transmit information to viruses that attach to cells via these receptors can cause infection. Most of the time there is no glycosylation on the membranes inside the cell however, it is more common for glycosylation to occur on the outer surface that is the plasma membrane.
• The glycocalyx is an essential element in all cells, particularly epithelia that have microvilli.
• Glycocalyx plays a role in lymphocyte adhesion, cell adhesion Homing, and many more.
• The final sugar is galactose, and the final syrup is sialic acid because the sugar backbone gets altered in the Golgi apparatus.
• Sialic acid is charged with the negative charge and acts as an external barrier for charged particles.

3. Proteins

• The cell membrane has two kinds of proteins that are associated with it that are known as Peripheral membrane proteins as well as Membrane Integral proteins.
• Membrane proteins from the peripheral membrane are external to and linked to the membrane through interactions with other proteins.
• Membrane proteins that are integrally incorporated introduced into the membrane. They are the majority of the proteins that are able to pass through the membrane. The transmembrane proteins are visible on both sides of membrane.
• Structural proteins aid in giving the cells support and shape.
• The cell membrane receptors assist cell membrane receptor proteins communicate with the environment by using neurotransmitters, hormones, and various other signaling molecules.
• Transport proteins, like globular proteins, move cells’ membranes via the process of diffusion.
• Glycoproteins are carbohydrate chains connected to them. They are embedded within the cell membrane and assist in cell-to-cell communication and also transporting molecules through the membrane.

Structure of Plasma Membrane Based on Fluid Mosaic Model of Membrane

1. Evolution of Fluid Mosaic Model of Membrane

Before the 1930s (when electron microscopy was introduced), it was difficult to demonstrate the existence of the plasma membrane of the cell through direct observation. The membrane exceeds the resolution of the light microscope, making a morphological approach to its investigation with this instrument absolutely impossible. Consequently, the majority of experimental procedures have revealed only indirect evidence of the existence of such a membrane around the cells. Let me briefly recount the evolution of the currently recognised fluid-mosaic model of plasma membrane structure:

• The plasmolysis of plant cells in hypertonic solutions indicates the presence of plasma membranes in plant cells.
• The fact that a cell, particularly an animal cell that lacks a cell wall, may exist as a physically distinct entity indicates that it must have some type of border.
• When an animal cell’s cell surface is ruptured, protoplasm can flow out, indicating the presence of plasma membrane.
• In 1899, after conducting over 10,000 trials with more than 500 distinct compounds. Overton concluded that the unique osmotic properties of live protoplasts are the result of a mechanism of selective solubility. Hydrophobic molecules penetrated cells faster than hydrophilic molecules. Overton felt that this was due to an outer lipoid layer that made hydrophobic molecules more soluble. He guessed accurately that this layer may include cholesterol, lecithin, and fatty oils.
• Hober (1910) and Fricke (1925) discovered that undamaged cells possessed low electrical conductivity, indicating the presence of a lipid layer.
• If a lipid containing hydrophilic groups (such as the carboxyl groups of fatty acids or the phosphate groups of phospholipids) is dissolved in a highly volatile solvent (e.g., benzene) and then carefully applied to the surface of water, the lipid spreads out to form a thin, one-molecule-thick or monomolecular film. This video reveals that the hydrophilic portions of each molecule extend into the water’s surface, whilst the hydrophobic portions are pointed upward, away from the water.
• In 1917, Langmuir (chemistry’s 1932 Nobel Laureate) created a trough or film balance for measuring the precise minimum surface area occupied by a monomolecular film of lipid and the force required to compress all the lipid molecules into this area. The Langmuir trough is a shallow, water-filled trough on which lipids can be dispersed to form a monomolecular film. To compress the film, one can push a barrier over the dip.
• In 1925, Gorter and Grendel isolated lipids from the erythrocyte ghosts of numerous mammals (including dogs, sheep, rabbits, guinea pigs, goats, and humans) and dispersed them over monolayers in the Langmuir trough. These researchers noticed that the lipid monomolecular layer film spanned twice the surface area of the cells from which it was taken. Consequently, they concluded that erythrocytes were covered by a layer of lipids two molecules thick (lipid bilayer or bimolecular lipid layer) orientated with polar groups facing the inner of the cell (lipid bilayer or bimolecular lipid layer).
• In 1935, Danielli and Davson devised a model for membrane structure known as the sandwich model, in which a lipid bilayer was coated on both sides with hydrated proteins (globular proteins). The stability of the membrane is believed to be maintained through mutual attraction between the hydrocarbon chains of the lipids and electrostatic interactions between the protein and the “head” of the lipid molecules. Based on the pace at which different molecules permeate the membrane, they anticipated the lipid bilayer to be around 6.0 nm thick and each protein layer to be approximately 1.0 nm thick, for a total thickness of approximately 8.0 nm. Electron microscopy validated the Danielli-Davson model. Electron micrographs of the plasma membrane revealed that it is composed of two dark layers (electron dense granular protein layers) that are separated by a brighter region (the central clear area of lipid bilayer). The total thickness of the membranes was also around 7,5 nm.
• Robertson, using evidence from numerous electron micrographs, suggested the unit memb-rane theory in 1960. This hypothesis asserts that the trilaminar structure of all cellular membranes is same (or dark-light- dark or railway track pattern, see Thorpe, 1984). However, the thickness of the unit membrane in plasma membrane (10 nm) was discovered to be larger than in intracellular membranes of endoplasmic reticulum or Golgi apparatus (i.e., 5 to 7 nm).
• S.J. Singer and G.L. Nicolson proposed the fluid mosaic model of biological membranes in 1972. According to this hypothesis (Fig. 5.5), the plasma membrane consists of a bimolecular lipid layer with protein molecules interspersed on both surfaces. In the form of globular molecules and dispersed in a mosaic pattern, proteins exist. Some proteins (i.e., extrinsic proteins) are connected to the polar surface of the lipid, whereas others (i.e., integral proteins) either partially penetrate the bilayer or traverse the membrane to protrude from both sides (called transmembrane proteins). In addition, peripheral proteins and those portions of integral proteins that adhere to the outer surface (i.e., ectoproteins) usually contain sugar or oligosaccharide chains (i.e., they are glycoproteins). Similarly, certain outer surface lipids are glycolipids. The fluid-mosaic membrane is believed to be considerably less stiff than was previously believed. Experiments on its viscosity indicate that it has a fluid consistency, similar to that of oil, and that the lipid and protein molecules inside it move significantly in the horizontal direction. This model of membrane construction is known as the “fluid mosaic model” on account of its fluidity and the mosaic arrangement of protein molecules (i.e., it describes both properties and organisation of the membrane). The fluid mosaic model is discovered to be applicable to all biological membranes, and its structure is viewed as dynamic and ever-changing. The proteins are not present to give the membrane strength; rather, they serve as enzymes that catalyse chemical reactions within the membrane and as pumps that transport substances across it.

2. Experimental Evidence in Support of Fluid Mosaic Model of Plasma Membrane

A substantial amount of evidence supports the fluid mosaic model of the plasma membrane:

A. Evidence in support of mosaic arrangement of proteins

• Branton’s (1968) freeze-fracture electron microscopy of the plasma membrane revealed the random distribution of bumps and depressions of 7 to 8 nm in diameter.
• It was later determined that they were transmembrane integral protein particles.

B. Evidence in support of fluid property of lipid bilayer

• A classic experiment by D. Frye and M. Edidin established the mobility of membrane proteins due to the fluid nature of lipid bilayer (1970).
• They combined two types of cultivated cells with distinct surface antigens (proteins).
• Utilizing a fusogen, such as an inactivated parainfluenza virus called Sendai virus, cell fusion is accomplished (named after a city of Japan). A fusogen is a factor that promotes membrane fusing, such as the Sendai virus, lysophosphatides, oleic acid, and an electric field. Sendai virus facilitates the union of the plasma membranes and cytoplasms of both cells, resulting in the formation of a hybrid cell or heterokaryon with two distinct nuclei. If the two cells are first marked with fluorescent antibodies of different colours, such as fluorescein (green) and rhodamine (red), it is feasible to identify the plasma membrane regions pertaining to each cell at the commencement of fusion. However, as the antigens are spread, intermixing occurs and the two colours become less and less distinguishable. After forty minutes (at 37 degrees Celsius), the intermixing of two colours is complete, and the two antigens are no longer distinguishable.

3. Role of Lipid Molecules in Maintaining Fluid Property of Membrane

(i) Types of movements of lipid molecules

• Very seldom do lipid molecules move from one monolayer of lipid bimolecular layer to another monolayer of lipid bimolecular layer. This form of movement is known as transbilayer or flip-flop movement, and it occurs once each month for every lipid molecule.
• In membranes where lipids are actively generated, such as smooth ER, there is a rapid flip-flop of particular lipid molecules across the bilayer, catalysed by membrane-bound enzymes known as phospholipid translocators (e.g., flippase).
• In contrast, lipid molecules shift positions with their neighbours within a monolayer approximately 107 times each second.
• This causes their rapid lateral dispersal. Individual lipid molecules rotate extremely rapidly about their long axes, and their hydrocarbon chains are highly flexible, with the highest degree of flexion occurring at the centre of the bilayer and the least degree of flexion occurring near the polar head groups.

(ii) Role of unsaturated fats in increasing membrane fluidity

• At a specific freezing point, a synthetic bilayer composed of a single type of phospholipid transforms from a liquid to a stiff crystalline or gel (viscous) state.
• This change in state is referred to as a phase transition, and the temperature at which it happens is reduced if the hydrocarbon chains are short or include double bonds.
• Unsaturated hydrocarbon chains with double bonds tend to increase the fluidity of phospholipid bilayers by making chain packing more difficult.
• In order to preserve membrane fluidity, cells of organisms living at low temperatures have a greater proportion of unsaturated fatty acids than cells living at higher temperatures.
• In reality, certain membrane transport processes and enzyme activity cease when the viscosity of the lipid bilayer exceeds a particular threshold. If, on the other hand, the fluidity of the lipid bilayer is enhanced, the membrane receptors for the hormone are pulled away from the cell surface, thereby inhibiting hormone function (see Sheeler and Bianchi, 1987).

(iii) Role of cholesterol in maintaining fluidity of membrane

• It has been discovered that eukaryotic plasma membranes contain a substantial quantity of cholesterol, up to one molecule per phospholipid molecule.
• Cholesterol molecules orient themselves in the lipid bilayer so that their hydroxyl groups remain close to the polar head groups of the phospholipids, while their rigid plate-like steroid rings interact with and partially immobilise those regions of hydrocarbon chains that are closest to the polar head groups, leaving the remainder of the chain flexible.
• Cholesterol prevents phase transition by inhibiting the coalescence and crystallisation of hydrocarbon chains.
• Cholesterol also tends to reduce the permeability of lipid bilayers to tiny water-soluble molecules and is believed to increase the bilayer’s flexibility and mechanical stability.

4. Membrane Asymmetry

This unusual distribution of lipid and protein molecules in both monolayers of the lipid bilayer is known as membrane asymmetry.

A. Phospholipid asymmetry in plasma membrane

• It is discovered that the lipid composition and fluidity of the two halves of a lipid bilayer are startlingly distinct. In the plasma membrane of the human erythrocyte, for instance, the outer half includes phospholipids with more saturated fatty acid chains, while the inner half contains phospholipids with terminal amino groups and less saturated fatty acid chains.
• Consequently, the inner lipid monolayer is more fluid than its outer counterpart. In smooth ER, this phospholipid imbalance is created.
• It has been discovered that the asymmetry of glycolipids such as galactocerebroside, ganglioside, etc. in the myelin sheath of neurons (i.e., they are exclusively found in the outer half of the lipid bilayer) originates in the lumen of the Golgi apparatus.
• The particular function of membrane lipid asymmetries is yet unclear.

B. Protein asymmetry in plasma membrane

• The outer and inner sides of the plasma membrane and other membranes, such as the plasma membrane of an erythrocyte, do not contain the same types or amounts of peripheral and integral proteins.

5. Constraints on the Motility of Membrane Molecules

• In the fluid mosaic plasma membrane, the distinct component molecules do not have complete and independent freedom of movement.
• The mobility of a portion of lipid molecules is restricted due to their tight association with integral membrane proteins.
• For instance, the enzyme immobilises the mobility of lipid molecules surrounding cytochrome oxidase (an enzyme involved in the generation of ATP) to form a border lipid layer.
• 30% of the membrane lipid in the mitochondrial membrane is composed of immobilised border lipid.
• In contrast to lipids, the mobility and distribution of protein molecules in the membrane are regulated by a number of mechanisms:
  • Certain membrane proteins are limited by protein-protein interactions to create organised sections comprising 2% to 20% of a system’s membrane, such as gap junctions, synapsis of neurons, and plaques of halobacteria.
  • Certain peripheral proteins (endoproteins) may form a bridge-like lattice work between integral proteins and restrict their lateral mobility, e.g., the spectrin-ankyrin-actin cytoskeletal meshwork of human erythrocytes provides membrane rigidity and prevents the clustering or capping of integral proteins when the appropriate antibodies or lectins are added.
  • Attachment to the ectoplasmic cytoskeleton restricts the mobility of peripheral endoproteins and integral proteins in nucleated eukaryotic cells.
• The vast cytoskeleton consists of myosin filaments, actin filaments, and microtubules.
• The redistribution of integral membrane proteins and the cellular movements endocytosis and exocytosis result from the rearrangement of cytoskeletal components directly under the cell surface.
• This is the intercellular space. In the tissues of multicellular animals, the plasma membranes of neighbouring cells are typically separated by a distance between 10 and 150 Ao.
• This intercellular region is homogeneous and contains a chemical with low electron density that can be regarded a cementing agent. This compound has been identified as a mucopolysaccharide.

Proteins of plasma membrane of erythrocytes

When the plasma membrane proteins of human erythrocytes (RBC) are analysed using SDS polyacrylamide-gel electrophoresis (SDS = sodium dodecyl sulphate; a detergent), approximately 15 major protein bands ranging in molecular weight from 15,000 to 25,000 are detected. The majority of these proteins have been identified as peripheral cytosolic plasma membrane proteins. The following are key characteristics of a few of these proteins:

(i) Spectrin and other cytoskeleton proteins

• Spectrin is the primary component of the protein meshwork (cytoskeleton) that lies beneath the plasma membrane of erythrocytes.
• Thus, it maintains the membrane’s structural integrity and biconcave form.
• Spectrin is a 100 nm long, long, thin, flexible rod. It comprises approximately 25% of the membrane-associated protein mass (about 2.5 x 105 copies per cell).
• Spectrin is a heterodimer composed of two non-identical, antiparallel, loosely intertwined, flexible polypeptide chains, i.e., –spectrin ( 240,000 daltons M.W.) and spectrin ( 220,000 daltons M.W. ), both of which are attached non-covalently to each other at multiple points, including their ends (i.e., phosphorylated ‘
• Self-association of spectrin heterodimers to create 200 nm long tetramers. The tail ends of five or six spectrin tetramers are connected by attaching to short actin filaments (also known as band 5 proteins; with a molecular weight of 43,000 dalton) and each with 15 actin monomers, as well as to another protein known as band 4.1 protein (82,000 dalton M.W.).
• These three proteins comprise the “junctional complex” of the cytoskeleton’s malleable, net-like meshwork.
• Additionally, the binding of spectrin cytoskeleton to the cytosolic face of the erythrocyte’s plasma membrane is dependent on the intracellular attachment protein ankyrin (or band 2.1 protein; 210,000 dalton M.W.).
• Ankyrin typically binds to both -spectrin and the cytoplasmic domain of band 3 protein, a transmembrane protein.

(ii) Glycophorin

• It is a tiny transmembrane glycoprotein (single-pass membrane protein) containing 131 amino acid residues and a molecular weight of 55,000 daltons.
• This protein contains around 100 sugars on 16 oligosaccharide side chains (90 per cent of which is sialic acid). Despite the fact that each erythrocyte contains more than 6 105 glycophorin molecules, their precise function remains unknown.
• glycophorins include particular antigenic determinants (carbohydrates) for ABO and MN blood types.
• Moreover, sialic acid imparts a strong negative charge to the erythrocyte cell surface. As it has been demonstrated that cells lose sialic acid as they age in the circulatory system, this sugar may play a significant role in the erythrocytes’ life cycle.
• Corresponding to this is the fact that the loss of sialic acid is a signal for the spleen and liver to remove and destroy an erythrocyte. This permits the regulation of the red blood cell lifespan.

(iii) Band 3 protein

• Band 3 protein (93,000 daltons M.W.), like glycophorin, is a transmembrane protein; however, it is a multipass membrane protein, meaning that its highly folded polypeptide chain (930 amino acids long) stretches across the lipid bilayer at least 10 times.
• Each individual human erythrocyte has around 106 and band 3 proteins, each of which forms a dimer or tetramer in the membrane.
• In the membrane, Band 3 protein functions as anion exchange channels. During the process of CO2 release, as erythrocytes move through the lungs, they exchange bicarbonate (HCO-) for chloride (Cl-) through these hydrophilic channels (chloride shift).

Origin of Plasma Membrane

• There is hardly a structure within a cell that is more vital to its immediate vitality than the plasma membrane.
• If the cell is damaged or harmed, it loses its ability to maintain gradients, transport nutrients selectively, and contain the pool of enzymes and organelles necessary for homeostasis.
• Thus, new membranes can be introduced to existing membranes without affecting their barrier and selective transporter capabilities.
• In order to preserve the characteristic asymmetry of the membrane, the membrane must also be built with the exact proper molecular topography.
• Consequently, all cellular membranes originate from pre-existing membranes that serve as templates for the insertion of new precursors.
• Daughter cells receive a full complement of membrane systems, which grow until the next division and are passed on to successive offspring.
• Meanwhile, the membrane’s molecules undergo continual replenishment. Plasma membrane protein molecules are produced on both connected and unbound ribosomes.
• Following their completion and release from the ribosomes, proteins produced by free ribosomes may be introduced into the plasma membrane.
• Plasma membrane proteins generated on attached ribosomes of rough ER are first inserted into the membrane of RER, then moved to the Golgi apparatus, processed there (e.g., glycosylation), and finally delivered to the plasma membrane via secretory vesicles.
• Similarly, phospholipid molecules of the plasma membrane are synthesised by the smooth ER (SER). Like newly generated proteins, newly synthesised lipids are inserted into SER membranes, transferred to the Golgi apparatus for processing, and finally sent to the plasma membrane via small secretory vesicles.
• In addition, the cytosol contains phospholipid transport proteins that move phospholipid molecules from one cellular membrane to another (e.g., from ER membranes to plasma membranes).
• In actuality, glycosylation (or glycosidation, i.e. the addition of oligosaccharides containing sugars such as galactose, fucose, and/or sialic acid to the molecules of plasma membrane proteins and phospholipids) is completed at the Golgi apparatus level. However, certain sugars are added to the RER lumen’s proteins.

Functions of Cell membrane

1. Selective Permeability

• Membrane membranes can be selectively permeable (or semi-permeable) this means they allow only specific molecules are able to traverse them. The oxygen, water carbon dioxide, and water can effortlessly pass across the membrane.
• In general the ions (e.g. sodium or potassium) and polar molecules are unable to traverse the membrane. they must pass through certain channels or pores within the membrane, instead of dispersing through.
• In this way, the membrane is able to control the speed that certain molecules be allowed to enter and leave the cell.

2. Physical Barrier

• The plasma membrane covers every cell and physically divides the cytoplasm which is the cell’s material, is the body of the cell and the fluid that is that is outside the cell.
• It shields the various components inside the cell against outside surroundings and allows for separate functions to take place within and outside of the cell.
• The plasma membrane offers structural support for the cell. It is the anchor for the cytoskeleton which is a system of protein filaments within the cell.
• They holds all the components of the cell. The cell’s cytoskeleton gives it its shape. Certain organisms , like mushrooms and plants have cells that have walls along with the membrane.
• The cell wall is made of cellulose-based molecules. It is a source of support for cells and is the reason plants don’t explode as animal cells do when there is too much water leaking into the cell wall.

3. Endocytosis

• Endocytosis refers to the process by the cells absorb molecules by taking them and engulfing them. The plasma membrane causes an inward-facing small deformation, known as an invagination, where the substance being transported is taken in.
• The invagination is caused by proteins located outside the cell membrane acting as receptors, and forming clusters into depressions, which eventually lead to the an accumulation of liquids and proteins on the cytosolic portion of the membrane.
• The deformation is able to pinch off the membrane within the cell, forming an elongated vesicle that contains the captured substance.
• Endocytosis can be described as a method of taking in solid particles (“cell eating” or the process of phagocytosis) as well as small molecules and ions (“cell drinking” or pinocytosis) and macromolecules. Endocytosis is a process that requires energy, and thus is an active form of transport.

4. Exocytosis

• As material is introduced into cells through invagination and the formation of a vesicle membrane of a cell can be joined to the plasma membrane and extrude its contents into the medium surrounding it. This is known as exocytosis.
• Exocytosis is a process that occurs in a variety of cells to clear the undigested residues of the substances brought in through endocytosis, and to release substances such as hormones or enzymes, and also to move substances completely across a cell barrier.
• When exocytosis occurs the waste that is accumulated in the food vacuole, or secretory vesicle, which is budded from the Golgi apparatus is initially transported by the cytoskeleton from cell’s interior towards the outer surface.
• The vesicle membrane is brought into close contact with plasma membrane. The lipid molecules in the two bilayers reorganize themselves in a way that both membranes become and are thereby joined.
• A passage is formed within the membrane that has been fused and the vesicles expel their contents to the outside of the cell.

5. Cell Signaling

• Another crucial purpose that the membrane serves is to aid in communication and signals between cells.
• It accomplishes this through the use of different proteins and carbohydrates within the membrane. The proteins on the cell “mark” this cell, so that other cells are able to recognize it.
• The membrane is also equipped with receptors that allow it to perform specific functions when substances like hormones or other hormones are bound to the receptors.

6. Compartmentalization

• Membranes are unbroken, continuous sheets, and as such, they always contain compartments.
• The plasma membrane encloses the entire cell’s contents, whereas the nuclear and cytoplasmic membranes envelop other intracellular regions.
• The contents of the numerous membranebounded compartments of a cell are notably distinct.
• Membrane compartmentalization permits specialised functions to proceed without external interference and facilitates the independent regulation of cellular activities.

7. Scaffold for biochemical activities

• In addition to enclosing compartments, membranes are also discrete compartments.
• Their interactions are depending on random collisions for reactants floating in solution.
• In contrast, components implanted in a membrane are no longer free to float and can be arranged for efficient interaction.

8. Transporting solutes

• The plasma membrane contains the machinery for physically moving substances from one side of the membrane to the other, typically from a location with a low solute concentration to a region with a much higher solute concentration.
• The transport system of the membrane enables a cell to amass chemicals, such as glucose and amino acids, required to power its metabolism and construct its macromolecules.
• Additionally, the plasma membrane can transport particular ions, so producing ionic gradients across itself.
• This capacity is particularly important for nerve and muscle cells.

9. Responding to external stimuli

• The plasma membrane plays a crucial role in signal transduction, the process by which a cell responds to external stimuli.
• Membranes contain receptors that bind to certain molecules (ligands) or respond to stimuli such as light or mechanical force.
• Diverse types of cells have membranes that contain different receptors, allowing them to recognise and respond to various environmental stimuli.
• When a plasma membrane receptor interacts with an external stimulus, the membrane may generate a signal that either stimulates or inhibits internal processes.
• For instance, plasma membrane-generated signals may instruct a cell to produce more glycogen, to prepare for cell division, to migrate toward a higher concentration of a certain substance, to release calcium from internal stores, or even to commit suicide.

10. Intercellular interaction

• The plasma membrane of multicellular animals, located at the outermost border of every live cell, mediates the interactions between a cell and its neighbours.
• The plasma membrane enables cells to detect and communicate with one another, adhere when necessary, and exchange materials and data.
• Additionally, plasma membrane proteins may enhance the interaction between extracellular materials and the intracellular cytoskeleton.

11. Energy transduction

• Membranes are closely involved in the processes that transfer one form of energy to another (energy transduction).
• During photosynthesis, the most fundamental energy transduction occurs when solar energy is absorbed by membranebound pigments, transformed into chemical energy, and stored as carbohydrates.
• The transfer of chemical energy from carbs and lipids to ATP also involves membranes. The machinery for these energy transformations is housed within the membranes of chloroplasts and mitochondria in eukaryotes.

Organelle Membranes

Organelles in cells are covered by protective membranes. The nucleus, endoplasmic-reticulum vacuoles, lysosomes and the Golgi apparatus are all instances of membrane-bound organelles. Mitochondria and chloroplasts , on the other hand, are bonded by two membranes. The membranes of different organelles differ in molecular structure and are designed for the tasks they play. Organelle membranes are essential to many vital cell functions like the synthesis of proteins, lipid production and cell respiration.

Models of plasma membrane

Fluid Mosaic Model (1972)

Description of plasma membranes is possible through an fluid model in terms of mosaic cholesterol, carbohydrates, proteins , and phospholipids.

In 1972, the model was first suggested in 1972 by Garth L. Nicolson and S.J. Singer The model was developed by Garth L. Nicolson and S.J. Singer to what the plasma membranes’ structure was. The model has evolved over time but is able to explain the function and structure of plasma membranes in the most effective method. The model defines the structure of plasma membranes as a mosaic of elements that includes cholesterol, proteins, phospholipids, carbohydrates, and proteins It also gives a fluid appearance to the membrane.

The thickness of the membrane is between 5-10nm. The percentage of constituency of plasma membrane i.e. the proteins, carbohydrates, and lipids differs from cell to. As an example, outer membrane of mitochondria is composed of 24 percent lipid and 76 percent protein. In myelin 76% of lipid is detected and 18 percent protein.

The principal fabric of this membrane is made up of phospholipid molecules which are amphiphilic. The hydrophilic regions of these molecules are in contact with the aqueous fluid on the outside as well as inside. The hydrophobic , or water hateful molecules on the contrary on the other hand, are not polar in the natural world. A phospholipid molecule consists of three carbons of glycerol’s backbone, two fat acid molecules that are connected with carbons 1, 2 and a phosphate-containing group that is connected by the 3rd carbon.

The organization provides a specific region known as the head to the molecule as a total. The head of the group that is phosphate-rich, has the polarity or negative charge whereas the tail, which is a separate area that is a source of fatty acids has no charge. They are more likely to interact with non-polar molecules during reactions, but are not able to connect with non-polar molecules.

When hydrophobic molecules are introduced into water, show the potential to form clusters. However, hydrophilic phospholipids are more likely to create hydrogen bonds with water , along the other polymers inside and outside of the cell. Thus, the membrane’s surface which interacts with the outside and inside of cells is classified as hydrophilic. However, the center of cell membranes is hydrophobic, and is not in contact with water. Thus, phospholipids are able to create a wonderful bilayer of lipids in the cell, which separates liquid inside the cell from the fluid that is on the outside that surrounds the cell.

The second component is created by the the plasma membrane. Integrins or integral proteins are integrated completely into the membrane’s structure together with their hydrophobic membrane. They range from hydrophobic regions to areas of the phospholipid bilayer. In general, single-pass integral membrane proteins have a transmembrane that is hydrophobic and consists of between 20 and 25 amino acids. A few of them traverse one portion of the membrane, connecting to a single layer, while others are able to span from one to the other aspect of membrane which exposes the reverse side.

Some complex proteins are composed of 12 segments of a single protein, which is extremely convoluted for placement in the membrane. This kind of protein is hydrophilic and has a region or two together with some mildly hydrophobic zones. The organization of these regions of proteins is likely to bring the proteins with phospholipids. The hydrophobic portion of the protein adjacent to the tails of hydrophilic regions and phospholipids of protein extends through the membrane and is in contact with the extracellular fluid, or cytosol.

The third major part of plasma membrane is the presence of carbohydrates. They’re typically located on the outside of cells and connected with lipids, forming glycolipids, or proteins to create glycoproteins. This carbohydrate chain could consist of two to sixty monosaccharide units, which can be straight or branched.

Carbohydrates in conjunction with peripheral proteins lead to the formation of areas on the surface of cells that recognize each with one another. This recognition is vital for cells because they allow your immune system differentiate between cells in the body and those of tissues and cells of foreign origin. Glycoproteins and glycoproteins are also present on the surface of viruses. They may differ, which can hinder immune cells from recognizing them and draw them.

On the outer surface that cells reside, sugars as well as their components of glycoproteins and glycolipids are named glycocalyx. This is extremely hydrophilic , and attracts huge amounts of water to the cell’s surface. This allows the cell to connect with the fluid surroundings and further enhances the ability of cells to absorb substances that dissolve in water.

Davson-Danielli model

• An observation that is consistent by plasma membranes that could not explained by the bimolecular model of lipid leaflets was the extremely minimal surface tension on the membrane.
• The year 1935 was the time when J. F. Danielli and E. N. Harvey suggested that oil droplets and other lipid inclusions inside cells were bound at their surface by a layered structure of lipids, as well as the protein layer.
• It was proposed that the proteins, composed of a monomolecular layered of molecules that were hydrated, faced the aqueous cell wall and connected with the polar parts that comprised the lipid layer.
• The nonpolar parts that comprised the lipid layers sat against the hydrophobic oil layer of the droplet’s inside.
• In this case it is believed that the normal surface activity of the protein will be the reason for the low interfacial pressure that forms the membrane around the droplet. Then, Danielli and H. Davson proposed that plasma could be made up of two bilayers of lipid-protein – one that faces the interior of the cell, and another facing outwards to the external environment.
• In this setup it is possible that the connection between surfaces proteins as well as the bimolecular lipid leaflet could be maintained by electrical interactions that occur between the two polar end of each lipid molecule as well as the amino acid charged side chains of polypeptide layers.
• Electrostatic or van der Waals bonds can bind other groups to the outer surface. Danielli and Davson suggested that such membranes would show specific permeability and be capable of distinguishing between molecules with different sizes and properties of solubility as well as between ions with different charges.
• In the 1950s, various modifications were made to the model of the Danielli-Davson membrane. For instance it was believed that glycoproteins could be absorbed by the membrane’s surface, thus explaining the antigenic characteristics that cell membranes exhibit. The pores through which certain substances are exchanged between cells and its surroundings were believed to exist. The channels created by regular continuousities (bridges) in the protein layers that are between the inner and outer layers.

Robertson’s Model

• According to Robertson the unit membrane was bimolecular lipid leaflets sandwiched between the inner and outer layers of protein arranged with pleated sheets.
• The arrangement was thought to be identical across every cell membrane.
• In the 1950s electron microscopy was used to provide additional information on what the shape of plasma membranes.
• J. D. Robertson was one of the pioneers in this field, demonstrating that membranes fixed using the osmium tetroxide had a distinct tri-laminar appearance , consisting of two distinct layers, the outer darker (osmiophilic) layers as well as an inner lighter (osmiophobic) layers.
• The osmiophilic layer typically measured between 20 and 25 A (2.0-2.5nm) on average, while the osmiophobic layers measured between 25 and 35 A (2.5-3.5 millimeters) with a final amount of about 65 to 85 A (6.5-8.5 millimeters). This number is comparable to the thickness that was predicted by chemical studies.
• Robertson and his colleagues demonstrated that the tri-laminar structure was common to many other cellular membranes that included the endoplasmic Reticulum. With regard to the fundamental uniformity in the appearance of cell membranes examined, Robertson proposed his now well-known unit membrane model of the unit membrane. According to Robertson the unit membrane was bimolecular lipid leaves sandwiched between the inner and outer layers of protein that were organized in the pleated sheet arrangement. The arrangement was thought to be the same across the cell membranes of all cells.
• Although Robertson acknowledged the distinct distinctions in the chemical composition of membranes (i.e. that the specific molecular species that comprise the membranes differ) Robertson believed the molecular pattern was fundamentally similar. While there is no doubt that the same electron microscopic appearance of a majority of membranes, an absolute chemical explanation to explain the uniformity of appearance is not viable anymore.
• Robertson has extended his model of the unit membrane to incorporate the idea that there is continuity between the layers of nuclear membranes as well as the plasma membrane through the endoplasmic retina. The existence of such continuity has been proven in studies using electron microscopy of a variety of tissues and cells.
• In addition, Robertson suggested that vesicular organelles could originate from this membrane system, and can be later pinched to form distinct structures. There is evidence to the direction of this idea with regard to micro-bodies and lysosomes.

Henderson as well as Unwin’s theory of the membrane

Henderson Unwin and Henderson Unwin have examined the purple membrane using electron microscopy using an approach to identify the projected structures of uncolored crystal specimens. Applying the technique to specimens that were tilted, and applying the concepts proposed by DeRosier and Klug to combine these two-dimensional images and 3D views, they have created a image of membrane with seven A resolution. The map shows the position of the lipid and protein components, the order of polypeptide chains inside each protein molecule, as well as the relationships between the proteins in the lattice.

High-resolution micrographs of crystal patterns of membrane proteins which were taken with a small amount of electrons in order to limit radiation damage, can be used to establish the 3-dimensional structure of the protein by using an Fourier transform. Recent studies of negatively stained rat liver cells Gap(tm) junctions that were subjected to three-dimensional Fourier reconstructions (of low-dose electron micrographs) reveal that the six sub-units of protein are placed in a cylinder tilted to the tangential, creating the channel to be 2 nanometers in width within the extracellular region. Dimensions of the channels inside the membrane were smaller, but were not able to be determined (Unwin and Zampighi 1980). A slight movement of the sub-units near the cytoplasmic end could decrease the tangential inclination of sub-units to a six-fold and thus end the channel.

More details on the molecular structure will emerge as more preparation methods are made available, ensuring that high-resolution 3-dimensional images similar to those of the membranes in purple are created. Utilizing ingenuous methods to analyze periodic arrays of macromolecules in biological systems that combine data from low-dose electron pictures along with diffraction patterns merged, Henderson and Unwin (1975) created a 3D model of the purple membranes with 0.7 millimeter resolution. The embedding of glucose was used to reduce dehydration-related damage, and low doses (less than 0.5 A*/e) to minimize radiation damage. The electron micrographs of stained membranes were recorded so that the sole reason for contrast is a small phase contrast that was induced by defocusing.

In their research, Unwin and Henderson found that the protein extends to each side of bi-layer of lipids and is comprised of seven a-helices arranged 1-1.2 millimeters apart, 3.5-4.0 inches in length and parallel to the membrane’s plane. The molecules are organised around a three-fold axis, with an area of 2 nm in the center, which is full of the lipids. This remarkable work is the most significant advancement so far, because it is the first time, provided researchers with the structural details of a membrane protein that is integral in the presence of. The amino acid sequence in conjunction with the details about electron scattering density derived from the research by Henderson and Unwin and others, has prompted models-building efforts (Engleman and colleagues. 1980) to integrate the sequence of bacteriorhodopsin into a set of A-helical segments.

Gorter with Grendel’s Membrane Theory (1920)

Evert Gorter and Francois Grendel (Dutch scientists) were the first to come up with our current model of plasma membrane as a bi-layer of lipids. They simply speculated that the plasma membrane could be bi-layered and the thickness of the monolayer is twice that of the surface area of plasma membrane. To test their hypothesis they conducted an experiment where the researchers extracted lipids out of an established amount of blood vessels (erythrocytes) from a variety of mammalian sourceslike sheep, goats and humans and so on. and then spread the lipids in a mono-layer inside a Langmuir-Blodgett tube. They examined the size of the plasma membranes that is composed of blood red cells and then using Langmuir’s method they measured the size in the monolayer the lipids. When comparing both, they came up with an approximate ratio of 2: mono-layer of lipids: Plasma membrane. This confirmed their theory that resulted in concluding that membranes of cells are made up of two distinct molecular layers. One of the scientists suggested a model of this bi-layer with the hydrophilic heads of the polar polar facing outwards toward the aqueous environment , and those with hydrophobic heads facing inside away from the surrounding aqueous environment to both the sides. Although they reached the right conclusion, certain aspects of the data were not correct, such as the incorrect estimation of the size and the pressure within the mono-layer of lipids and the lack of completeness in the extraction of lipids. They also did not adequately describe the function of membranes, and made incorrect assumptions, such as those of plasma membranes made up of mainly the lipids. On the other hand, in general this conception of bi-layer structure of lipids became the fundamental assumption that underlies each subsequent refinement in our knowledge of the function of membranes.

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References

• https://www.genome.gov/genetics-glossary/Cell-Membrane#:~:text=The%20cell%20membrane%2C%20also%20called,entering%20and%20exiting%20the%20cell.
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