Archives for category: BioMembrane

3- Transport by vesicles: when proteins are made on the rough endoplasmic reticulum (RER), they get loaded into the Golgi apparatus. They are then sorted, modified and packaged in vesicles made from the budding-off of the Golgi membrane and discharged.

Sorting signals directs the protein to the organelle. The signal is usually a stretch of amino acid sequence of about 15-60 amino acids long.

There are at least three principles that characterize all vesicles mediated transport within cells:

                      i.        The formation of membrane vesicles from a larger membrane occurs through the assistance of a protein coat such as clathrin that engulfs the protein because an adapter protein such as adaptin binds both to the coat and to the cargo protein bringing both close together.

Clathrin-coated vesicle transport. Click on image for credit.

The adaptin traps the cargo protein by biding with it’s receptors. After assembly particles bind to the clathrin protein they assemble into a basket-like network on the cytosolic surface of the membrane to shape it into a vesicle. Their final budding-off requires a GTP-binding protein called dynamin.

                    ii.        The process is facilitated by a number of GTP-binding proteins (ex; dynamin) that assemble a ring around the neck of a vesicle and through the hydrolysis of the phosphate group of GTP to GDP until the vesicle pinches off. In other words, GTP is one of the main sources of cellular energy for vesicle movement and fusion.

Dynamin powered by GTP pinches the vesicle off the membrane. Click on image for credit.


Another picture of the same process. Click on image for credit.

                   iii.        After a transport vesicle buds-off from the membrane, it is actively transported by motor proteins that move along cytoskeleton fibers to its destination. The vesicle then fuses with a target membrane and unloads the cargo (protein). But in order to fuse a vesicle with the membrane of another compartment, they both require complementary proteins, which in this case is soluble N-ethylmalei mide-sensitive-factor attachment protein receptor or, ahem, SNARE present in the membrane – one for the vesicle (vesicular SNARE) and one for the target membrane (t-SNARE).

SNARE helping direct transport vesicles to their target molecules. Click on image for credit.

Each organelle and each type of transport vesicle is believed to carry a unique SNARE. Interactions between complementary SNAREs helps ensure that transport vesicles fuse only with the correct membrane.

Membrane fusing does not always follow immediately after docking (unloading of cargo), however it often waits for specific molecular signals.

Btw, based on coat protein, transport proteins can be classified into three types:


Coated Vesicle Types.

COP stands for Coatamer proteins (COP) which is the second class of coat protein that mediates budding-off of vesicles from large membranes. It can be of two types I (anterograde; moving in a forward direction. Ex; from ER to Golgi) & II (retrograde; moving in a backward direction. Ex: from Golgi back to ER).


2-  Transport across membranes: Similar to how transport functions via the nucleus, most proteins are transported across the biomembrane with the help of receptor proteins which form a complex with the import molecule.

Protein translocators located between the biomembrane (transmembrane protein or integrins) identifies the signal sequence by unfolding the protein and transports it across the membrane into the organelle or cell (similar to the way NPCs do).

Once the protein enters the organelle or cell, its signal sequence is cut off by a peptidase enzyme and the protein is folded into its final 3-D shape again with the help of helper molecules.


In the case of proteins intended for secretion out of the cell, as soon as their N-terminal contains the signal sequence that will indicate this, a signal recognition particle binds to it and forms a protein complex causing synthesis to slow down. The SRP-protein complex will travel and bind to a SRP-receptor on a rough endoplasmic reticulum (RER) membrane. Once the protein gets to the RER membrane, its synthesis will continue at the normal rate until it is complete. During translocation out of the cell, the signal sequence is cut off by a signal peptidase located in the RER membrane and released from the translocation channel and degraded to amino acids.

RER serves as an entering point for proteins that have to go to other organelles like the Golgi complex and lysosome. They can also ferry proteins out of the cell by transport vesicles formed from the budding off of their biomembrane.


There are three mechanisms in which newly synthesized proteins are inserted into the RER membrane (the mechanisms vary with the type of protein);

  • Type I; signal sequence on N-terminals enters first and continues to elongate until a hydrophobic stop-sequence is reached, and then inserted in the membrane and forms the anchor for that protein. Of course then signal sequence is cut by protease.
  • Type II; these proteins have rather long hydrophobic regions that will be anchored in the membrane with the C-terminal leading. Protein continues to be inserted until it reaches the hydrophobic stop-sequence, but the signal sequence is not cut.
  • Type III; same as type I, the only difference is that the signal sequence is not cut.


And according to the number of times that protein passes through the membrane, the proteins of the ER membrane can be divided into single pass transmembrane protein, double pass transmembrane protein, and multi-pass transmembrane protein.


I understand the information here may appear bland. This is because it has been generalized for most process within the cell and cell biologists study the various pathways that exist which can be very overwhelming. Here a brief overview is being discussed such that when you choose to do more detailed study, this generic pattern would have provided you with a basic background.

Extracellular matrix (ECM) is the material found around cells and biochemically partly made by the cell. It is composed of complex mixtures of proteins, proteoglycans, and, in the case of bone tissue, contains mineral deposits as well.

  • Protein; almost all of the proteins found in the ECM are glycoproteins which include any of a group of complex compounds containing sugar units or polysaccharides combined with amino acid units or polypeptides. Some examples are collagen, laminin and fibronectin. Elastin is not a glycoprotein but is simply a protein and provides flexibility to skin arteries and bones.
  • Proteoglycan; are partially similar to glycoproteins but are made up mostly of carbohydrate consisting of various polysaccharide side chains linked to a protein, and resemble polysaccharides rather than proteins in their properties. They usually have groups of carbohydrate chains attached to a protein backbone.

    Typical Proteoglycan. Click on image for credit.

  • Mineral deposits; found in bones such as calcium and phosphorous.

Most normal cells cannot survive unless they are anchored to the extracellular matrix.

Cells attach to the ECM by means of integrin (integral membrane proteins) which are transmembrane glycoproteins that bind to the ECM proteins collagen, laminin and fibronectin (can exert a physical force on the cell). Internally, the integrin binds to actin filaments of the cytoskeleton. This gives them a key structural role in cells (more on this in chapter 6).


Cells don’t simply squeeze next to each other in a tissue because if they did, they might temporarily hold together but wouldn’t be stable enough to compose tissue as they’d fall out due to lack of adhesion. They are connected to each other via membrane-associated structures (structures situated on the plasma membrane), usually transmembrane proteins. These membrane-associated structures help in cohesion and communication. Where cells stick tightly to each other (adhesion), this is done with the help of Cadherins, a family of transmembrane glycoproteins. Not only does it stick cells together, it also helps seal junctions between cells to prevent the flow of materials through the intercellular space.

There are many types of intercellular junctions situated at various spots on the cell:

1. Tight Junctions or Zonulae Occludens (singular Zonula) situated apically. Zonula is Latin for encircling and Occludensto enclose- so referring to the fact that the junction forms a band completely around the cell fusing cells together and closing-off intercellular space. The number of fusion sites (viewed as ridges and grooves like a suture) often correlate to the leakiness of the cell tissue. The less fusion sites, the more permeable to water and solutes and vice versa. Ex; Cells of the proximal renal tubule of the kidney where filtration often takes place have few fusion sites to allow for leakability, whereas, cells of the urinary bladder (that must hold urine and not allow it to leak out) contains numerous fusion sites or tight junctions to form a seal to prevent the flow of materials between epithelial cells.

Intercellular Junctions. . The cell in the middle was emptied of it’s contents to show the inner surface of it’s membranes.


2. Intermediate Junction or Zonulae Adherens situated at close proximity to the apex but somewhat below the tight junctions, also encircles the cell and provides adhesion of neighboring cells to each other due to the insertion of numerous actin filaments from the cytoplasm of the cell into the junction forming a network. But, unlike tight junctions, they are relatively permeable as there are no fusion sites that completely seal off the paracellular space. The two Zonulas form a continuous ribbon around the cell apex.


3. Gap junction situated almost anywhere along the lateral surface of the epithelial cell is simply a gap between the neighboring cell membranes that is about 2nm. Contains protein unit called connexin (a hexamer: polymer made of six monomers) with a hydrophilic pore (1.5nm diameter) that acts as a hydrophilic ion channel between two cells. Thus, an individual unit of the gap junction is called a connexon (many seen in image).

Connexons. Gap Junction.


4. Desmosome or Macula Adherens can be situated anywhere on the lateral surface (or sides) as well. Macula means a patch so it doesn’t take the length of the membrane and unlike the Zonulas, does not surround the cell. It is a disk-shaped structure matched with an identical structure at the surface of the adjacent cell made up of 12 proteins (circular attachment plaques or spots). The membrane in this region are straight and usually further apart (30nm). It’s adhesion function is further empowered by groups of intermediate keratin filaments which provides firm adhesion.


5. Hemidesmosome literally means half a desmosome. It is also a Macula or plaque or spot of adhesion but between the basal surface of cells and their basal lamina (layer made of connective tissue usually present under cells in tissue). So in effect, the Maculais only on one side.

Intercellular Junctions.


From a functional point of view, therefore, junctions between cells can be classified as adhering junctions (zonula adherens, desmosome and hemidesmosome), impermeable junctions (zonula occludens) and communicating junctions(gap junctions).


Intercellular Junctions Summary Classification.


Additionally, as mentioned earlier, intergrins are receptor proteins that both bind to and respond to the ECM in different ways such as wound healing, cell differentiation (chapter 10), and apoptosis (chapter 11).

In terms of permeability, water, dissolved gases such as carbon dioxide and oxygen and lipid solid molecules simply diffuse across the phospholipid bilayer because the fluidity permits them.

Water soluble anions (negative ions) generally pass through small horns less than .8 nm in diameter (.0000000008m; 1m=1000mm, 1mm=1000µ-micrometer, 1µm= 1000nm). However, all other larger molecules require carrier molecules or proteins to transport them through the membrane.


The following are an overview of the four different ways in which atoms and molecules cross the biomembrane, which is also called transmembrane transport:


  • Simple diffusion; is the process by which small molecules and ions simply, because of their tendency to spontaneously move around, especially from a region where they are highly concentrated towards a region where they are less, diffuse through the phospholipid bilayer of the biomembrane.


  • Facilitated diffusion; is the process by which, apart from water and ions, specific molecules such as monosaccharides and amino acids, diffuse through channel proteins down their concentration gradient. This assisted diffusion provides them with a special hydrophilic pathway since some molecules might resist the hydrophobic core of the phospholipid bilayer. Some specific ion channels remain open much of the time and are called nongated channels and others only open in response to specific chemical or electrical signals and referred to as gated channels, including the voltage-gated channels of the nervous system which transmit action potentials (nerve impulses) to the brain.


  • Active Transport; is the transmembrane transport that occurs when channel proteins, such as the enzyme ATPases (enzymes usually have the suffix –ase) use the energy of ATP hydrolysis (breaking one phosphate group from the nucleotide Adenosine triphosphate) to move ions or small molecules across a membrane against their chemical concentration gradient or electric potential gradient or both.


General Principle of ATP hydrolysis. Breaking bonds usually give off energy.


ATP-powered pumps which requires energy, is coupled to the hydrolysis of ATP and the overall reaction– ATP hydrolysis and the “uphill” movement of ions or small molecules- is energetically favorable. All ATP-powered pumps are transmembrane proteins with one or more binding sites for ATP located on the cytosolic face of the membrane.

Sodium/Potassium ATP Powered Pump.

Although these proteins commonly are called ATPases, they normally do not hydrolyze ATP into ADP and Pi unless ions or other molecules are simultaneously transported. Because of this tight coupling between ATP hydrolysis and transport, the energy stored in the phosphahydride bond (bond between two phosphate groups) is not dissipated but rather used to move ions or other molecules uphill against an electrochemical gradient.


  • Cotransporter; are also enzymes. They mediate coupled reactions in which an energetically unfavorable reaction, such as the movement of molecules or ions against their concentration gradient, is coupled to an energetically favorable reaction such as the passive transport of molecules down their concentration gradient. The co-transporter will use the energy of the passive movement to actively transport other molecules up their concentration gradient. Therefore, unlike ATP, two molecules have to always move through the co-transporter at one time.


This Cotransporter is a Symporter. More below. Click on image for credit.

 The co-transporter is sometimes referred to as secondary-active transporter because it uses the energy stored into an electrochemical gradient.

Cotransporters fall into two types:

1-            Antiporter: in which the movement of both molecules (energy favorable and unfavorable) are in opposite directions.

2-            Symporter: in which the movement of both molecules are in the same direction (see above image). This should not confuse you because the same principle applies- one molecule will be moving down its concentration gradient, and the energy in this will be used to actively move another molecule up its concentration gradient but in the same direction, similar to the Sodium/Potassium pump but without the need for ATP hydrolysis because the Cotransporters are smarter and more efficient than Active transporters or ATPases.

Membrane fluidity needs to be maintained for the cell to function normally, example, when red blood cells try to squeeze through blood capillaries. Also, fluidity allows small molecules to diffuse rapidly through and aids cell movement, growth, division etc.

Apart from temperature, one important factor for fluidity is the length of the hydrocarbon tail of the phospholipid in the bilayer which determines the stability and fluidity of the biomembrane. The longer the chain length of the tail, the more likely the hydrocarbon tails will interact with one another forming a secure and rigid structure.

Another factor is the degree of unsaturation of the hydrocarbon tail of the phospholipid in the bilayer. The chain that has a double bond does not have the maximum number of hydrogen atoms and the double bond creates a small kink in the hydrocarbon tail (chapter 2, lipids) which makes it more difficult for the tail to pack against one another and therefore more space for movement.

Additionally, certain types of movement within the membrane are more frequent than others;

Lipid Movement.

  1. Lateral Diffusion; molecules of the biomembrane simply transpose with neighboring molecules.
  2. Rotation; is when an individual lipid molecule rotates very quickly around its axis (up to 30’000 rotations per minute).
  3. Swing; from side-to-side.
  4. Flexion; contraction movement.
  5. Transverse Diffusion; also known as flip flop, is a movement of molecules from one half of a mono-layer to the other. The reason why flip flop happens less often is because the hydrophilic head of the lipid must go cross the internal hydrophobic sheet to go to the other mono-layer and faces a lot of friction. Flip flop is usually facilitated with the help of enzymes called flippases.

Because of flippases, different types of phospholipid molecules (Examples: Sphingomyelin, phosphatidylcholine, phosphatidylserine, phosphatidylethanol-amine, phosphatidylinositol and cholesterol) become concentrated in each monolayer making the bilayer asymmetrical. The two halves of the bilayer contain very different types of phospholipids and glucolipids, and the proteins of the bilayer have different orientations.

Example of asymmetry in the phospholipid bilayer of the biomembranes.

All these add up to create a highly diverse and fluid biomembrane.

3. Apart from membrane-lipids and membrane-proteins, the final basic component of a biomembrane is membrane-carbohydrates. However, they do not exist in isolation, rather in combination with membrane-lipids to form glucolipids/glycolipids, or combine with membrane-proteins to form glucoproteins/glycoproteins. The combination happens via covalent bonds.

Membrane-Lipids and -Proteins. Click on image for credit.

Most membrane carbohydrates are located on plasma membranes and have the following functions:

  • Improve the stability of membranes.
  • Advance the fastness and activate proteinase (protein enzymes which hydrolyze proteins into polypeptides) in the extracellular matrix.
  • Help membrane-proteins form correct three-dimensional configurations.
  • Take part in cell signal recognition, cell adhesion and cell junction (more detail later).
  • Correct the position and orientation of new proteins for transfer.
  • Lectin, a glucoprotein, protects the cell. So they also aid in protection.
  • Glucolipids act as blood groups determinants because some function as cell recognition particles.

I understand that stating these important roles is not enough to fully comprehend their significance. Later chapters will deal with the details. This is simply a fleeting reference to their roles.

In general, according to their main functions proteins and glycoproteins can be classified to five types:

  1. Channel proteins to form pores for the free transport of small molecules and ions across the membrane (more in Chapter 4).
  2. Carrier proteins to facilitate diffusion and active transport of molecules and ions across the membrane (more in next post).
  3. Cell Recognition Proteins; identifies a particular cell or gives them identity (more in Chapter 7).
  4. Receptor proteins; binds with specific molecules such as hormones and cytokines and gets activated to perform a specific function (also more in chapter 7).
  5. Enzymatic proteins; catalyze specific chemical reactions.
I think it is becoming clear that proteins are really important macro molecules and that most of animal cell biology will discuss it’s various functions.

All cells are surrounded by a layer of membrane that separates their internal environment (cytoplasm) from the external environment (exoplasm or extracellular matrix). Additionally, the organelles in cells, as explained earlier, are compartmentalized with the help of bio membranes, with similar chemical composition as that of the plasma membrane.

The membrane-enclosed organelles in the cytoplasm of cells (apart from the cell itself and the nucleus) are endoplasmic reticulum, Golgi apparatus, lysosome, vacuole, chloroplasts and mitochondria. So it is very important for us to understand the structure and chemical composition of the biomembranes.

Cell Structure. Click on Image for Credit.

Biomembranes are made of three types of macromolecules (one in each post :):

  1. The Lipid Bilayer which is largely made of phospholipid; (we’ve discussed earlier) a glycerol molecule is joined to two fatty acid chains and the third site on the glycerol is linked to a hydrophilic phosphate group. Phospholipids are therefore amphipathic lipids, meaning they are partly water soluble and partly insoluble. This is because they have both hydrophobic (fatty acid tail) and hydrophilic (phosphate group) regions.

Phospholipid. Click on Image for Credit.

In order to understand the lipid bilayer structure of a cell, hypothetically imagine its development- If we try to dissolve one phospholipid in a water molecule, the hydrophilic head (which contains the phosphate group) will dissolve in the water, whilst the hydrophobic tail will remain outside the water. However, if two or more phospholipids get together, they will start forming a different structure; the heads will still dissolve in water, but the tails, rather than facing outwards, will face inwards towards each other shielding the water out.

Lipid Bilayer Formation. Click on Image for Credit.

This molecular character causes phospholipids to form a spherically bilayer structure called liposome. In it, all nonpolar tails in each phospholipid molecular layer is called a leaflet. Examples of phospholipids are phosphatidylcholine (the phosphate group is attached to a second small hydrophilic compound such as choline. See first image) and sphingomyelin.

Because the lipid bilayer has a nonpolar hydrophobic core that is not easily permeable, biomembranes are interspersed or separated by proteins (referred to as membrane proteins) that allow certain molecules and ions to pass and so act as gateways or pathways towards and outwards the cell cytoplasm. The best analogy here is that of a concrete house interspersed with windows and doors to allow passage of people and air.

Fluid Mosaic Model. Click on Image For Credit.

Structurally, the plasma membrane is referred to as having a Fluid Mosaic Model. This refers to the story of Prophet Moses (Mosaic) parting the sea, and crossing over. The protein gateway here provide that effect.

Cholesterol is another lipid molecule that is present in the biomembrane. It consists of four hydrocarbon rings (that are strongly hydrophobic) and a hydroxyl group (O-H) attached to one end and is weakly hydrophilic. This quality makes cholesterol amphipathic as well.

One of its main functions is that it can break down the tight connection of the biomembrane phospholipid bilayer making it more flexible for the passage of small molecules and ions. Because of this and the fact that phospholipids have the capacity of movement within the biomembrane (more on this later), it explains the presence of “fluid” in the Fluid Mosaic Model.

In the electron microscope, the cell membrane appears to have a trilaminar appearance (having three layers):

Electron Microscopy of Plasma Membrane. Click on Image For Credit.

Two dark bands indicating the lipid bilayers of the hydrophobic tail and one bright band showing the intramembranous space between the bilayers. The hydrophilic core or polar head is not visible because it has dissolved in water.