Cell Biology

CELL MEMBRANE

Cell membranes are an essential component of the cell, providing separation between the intracellular and extracellular environment. They are composed of lipids, proteins and carbohydrates. See History of the Cells.

STRUCTURE

Phospholipids

The membrane bilayer contains many kinds of phospholipid molecules, with different sized head and tail molecules. These consist of a head molecule, a phosphate molecule, a glycerol and two fatty acid chains. Head group- This is a polar group e.g., a sugar or choline – meaning that the head end of the phospholipid is hydrophilic. Tail of 2 fatty acid chains – normally consisting of between 14-24 carbons (but the most common carbon lengths are 16 and 18). If the chain contains a cis double bond, then the chain is kinked – therefore reducing the tight packing of the membrane and so increasing its movement. As the tail is made of fatty acids, it does not form hydrogen bonds with water and therefore is hydrophobic and non-polar. Phospholipid molecules are therefore amphipathic – being both hydrophilic and hydrophobic. They spontaneously form bilayers in the water with the head groups facing out and the tail groups facing in. In the bilayer, there are van der Waal forces between the fatty acid tails of the phospholipid, with electrostatic and hydrogen bonds between the hydrophilic groups and water.

Cholesterol

Cholesterol is vital for many functions in a cell, including very importantly, a major constituent of the cell membrane. Cholesterol itself consists of a polar head, a planar steroid ring and a non-polar hydrocarbon tail. Cholesterol is important in the membrane as it helps to maintain cell membrane stability and fluidity at varying temperatures. Cholesterol is bound to neighboring phospholipid molecules via hydrogen bonds and therefore at low temperatures, reduces their packing. Overall, this means at low temperatures, when rate of movement is lowest, a fluid phase is maintained. At high temperatures, cholesterol helps to stop the formation of crystalline structures, and the rigid planar steroid ring prevents intrachain vibration and therefore making the membrane less fluid.

Membrane Proteins

As was shown in the table above, a typical cell membrane consists of around 60% protein. There is such a high proportion of protein because they are so vital in almost every process within a cell. A list of just a few functions of membrane proteins could include:

·         Catalysts – enzymes.

·         Transporters, pumps and ion channels.

·         Receptors for hormones, local mediators and neurotransmitters.

·         Energy transducers.

More active cells or organelles e.g., mitochondria, tend to contain more proteins, showing again that specialization of function determines structure. As part of the cell membrane, proteins can either be deeply embedded within the bilayer (integral) or be associated with the surface of the cell (peripheral).

FUNCTIONS OF THE CELL MEMBRANE

Cell membranes are vital for the normal functioning of all the cells in our bodies. Their main functions consist of:

1. Forming a continuous, highly selectively permeable barrier – both around cells and intracellular compartments.

2. Allowing the control of an enclosed chemical environment – important to maintain ion gradients.

3. Communication – both with the extracellular and extra-organelle space.

4. Recognition – including recognition of signaling molecules, adhesion proteins and other host cells (very important in the immune system).

5. Signal generation – in response to a stimulus creating a change in membrane potential.

In a cell, different parts of the membrane have different functions and therefore their structure is specialized for this. An example of this specialization can be seen in the different parts of a nerve; the cell membrane in the axon is specialized for electrical conduction whereas the end of the nerve is specialized for synapsing, meaning the composition of the membrane is different.

THE NUCLEUS

It is a membrane bound organelle found in the majority of eukaryotic cells. It is the largest organelle of the eukaryotic cell, accounting for around 10% of its volume. It houses the genome, and through gene expression, it co-ordinates the activities of the cell.

STRUCTURE

The nucleus is a relatively large and spherical membrane-bound organelle. The nucleus itself is comprised of distinct components, and understanding their structure allows a deeper understanding of their function.

Nuclear envelope

The nucleus is completely surrounded by the nuclear envelope. This consists of both an inner and outer membrane which run parallel to each other. The envelope is perforated by small gaps known as the nuclear pores. These pores are around 100nm wide in true diameter, however due to the presence of central regulatory proteins the true size of the gap is around 9nm. This small size controls the passage of molecules into and out of the nucleus. Larger molecules such as larger proteins and nucleic acid are unable to pass through these pores, and so the function of the nuclear envelope is to selectively separate the contents of the nucleus from that of the cytoplasm.

Nuclear lamina

Mechanical support for the nucleus is provided by the nuclear lamina. This is a protein mesh, which is more organized on the internal surface on the nucleus than on the cytoplasmic surface.

Chromatin

Chromatin describes DNA that is complexed with proteins. The primary protein components of chromatin are histones, which are highly basic proteins that associate readily with DNA. Histones combined with DNA form nucleosomes, which are the subunit of chromatin. Specifically, a nucleosome describes a segment of DNA associated with 8 histone proteins. By associating with histones, DNA is more compact and able to fit into the nucleus. Chromatin can exist as either euchromatin or heterochromatin. Euchromatin is the form of chromatin present during gene expression and has a characteristic ‘beads on a string’ appearance. It is activated by acetylation. In contrast, heterochromatin is the ‘inactive’ form and is densely packed. On electron microscopy, euchromatin stains lighter than heterochromatin which reflects their relative densities.

Nucleolus

The nucleolus is the site of ribosome and ribosomal RNA production. On microscopy, it appears as a large dense spot within the nucleus. After a cell divides, a nucleolus is formed when chromosomes are brought together into nucleolar organizing regions. During cell division, the nucleolus disappears.

FUNCTION

1. Cell compartmentalization: The presence of a selectively permeable nuclear envelope separates the contents of the nucleus from that of the cytoplasm.

2. Gene expression: Gene expression first requires transcription, which is the process by which DNA is transcribed into mRNA. As the nucleus is the site of transcription, proteins within the nucleus play a key role in regulating the process.

3. Processing of pre-mRNA: Newly synthesized mRNA molecules are known as pre-mRNA. Before they exit the nucleus, they undergo a process known as post-transcriptional modification where molecules are added or removed from the structure.

THE ENDOPLASMIC RETICULUM

It is the major site of synthesis in the cell. It is a system of flattened sacs (cisternae) that are continuous with the outer nuclear envelope. Its physiological function has a very close association with that of the Golgi apparatus and together, they form the secretory pathway of the cell. The endoplasmic reticulum is classified as either rough or smooth, with minor variations in size and function in specialized tissue. In this article, we will look at the structure and function of the rough and smooth endoplasmic reticulum and consider some clinical relevance.

ROUGH ENDOPLASMIC RETICULUM (RER)

The rough endoplasmic reticulum (RER) takes its name from the many ribosomes attached to the cytoplasmic surface. The RER takes developing proteins from the cytosol and continues their development prior to completion in the Golgi apparatus. Proteins that move across the membrane of the RER undergo a series of post-translational modifications, including the addition of signal sequences to target them to the correct part of the cell. Cells that produce many secretory proteins will have will extensive RER and mitochondria. The RER plays an important role in the synthesis of proteins that are destined for:

• Secretion into the extracellular matrix e.g., mucus and enzymes.

• Association with the cell membrane e.g., receptors and channels.

• Membrane bound vesicles e.g., enzymes of lysosomes.

Part of the modification process involves the folding of developing proteins. Correctly folded proteins are transported to the Golgi for secretion. Incorrectly folded proteins are kept within the cell and eventually destroyed. Despite the presence of ribosomes being such a defining feature of RER, RER-ribosomal interactions are not permanent and thus go through periods of attachment and detachment depending on the demand for protein secretion. Adhesion to the surface is energy dependent and so we see ribosomes detach in hypoxic cell injury when ATP/GTP synthesis is reduced.

SMOOTH ENDOPLASMIC RETICULUM (SER)

The smooth endoplasmic reticulum is important in the synthesis of lipids, phospholipids and steroids. It is often less extensive, and ribosomes do not associate with it, though certain specialized tissues (e.g., steroidogenic cells and muscles) often have extensive SER. They also contain cytochrome P450 enzymes which are important in the metabolism of certain drugs and toxins e.g., alcohol and barbiturates. Hepatocytes store glycogen in regions that are rich in SER. Smooth endoplasmic reticulum found within muscle is known as the sarcoplasmic reticulum and serves a specialized function.

SARCOPLASMIC RETICULUM

The SER in muscle is extensive because it plays a major part in the sequestration of calcium, which modulates the tonic force of contraction (and relaxation). The ultrastructure of the sarcoplasmic reticulum differs between muscle types. In striated muscle, they are arranged around the perpendicular T tubule, where the action potential/ surface Ca2+ inflow can initiate the calcium spike. This gives rise to the diads (cardiac muscle) and triads (skeletal muscle). Different types of muscles have different extensiveness of SR.

THE GOLGI APPARATUS 

It is a membrane bound organelle found in most cells. It is responsible for packaging proteins into vesicles prior to secretion and therefore plays a key role in the secretory pathway.

STRUCTURE

The Golgi is made of 5-8 folds called cisternae. The cisternae contain specific enzymes creating five functional regions which modify proteins passing through them in a stereotypical way, as follows:

1. Cis-Golgi network: faces the nucleus, forms a connection with the endoplasmic reticulum and is the entry point into the Golgi apparatus.

2. Cis-Golgi: major processing area allowing biochemical modifications.

3. Medial-Golgi: major processing area allowing biochemical modifications.

4. Trans-Golgi: major processing area allowing biochemical modifications.

5. Trans-Golgi network: exit point for vesicles budding off the Golgi surface, packages and sorts biochemicals into the vesicles according to their destination.

 FUNCTION

The Golgi apparatus modifies proteins and lipids that it receives from the endoplasmic reticulum. These biochemicals leave the Golgi by exocytosis before being delivered to different intracellular or extracellular targets.

• Protein processing – carbohydrate regions of glycoproteins are altered by addition, removal or modification of carbohydrates.

• Lipid processing – adds phosphate groups and glycoproteins to lipids from the endoplasmic reticulum (such as cholesterol) to create the phospholipids that make up the cell membrane.

SORTING, BUDDING AND EXOCYTOSIS

Biochemicals are chemically labelled in the Golgi to ensure appropriate delivery to the correct destination. Once they bud off the trans-Golgi, they will enter a specific pathway according to this signaling sequence.

• Lysosomal proteins – such as enzymes are packaged into specific vesicles. These proteins are typically tagged with mannose-6-phosphate in the Golgi

• Secretory proteins – such as hormones are packaged into secretory vesicles ready for exocytosis. This requires ATP as two negatively charged membranes need to fuse to allow their release. The membrane of the vesicle will form part of the cell membrane. This is only possible in Golgi of secretory cells.

• Cell surface proteins – such as phospholipids enter the constitutive secretory pathway present in all cells.

LYSOSOMES

They are spherical, membrane bound organelles that are generated by the Golgi apparatus. They contain hydrolytic enzymes and so function as part of the recycling system of the cell.

STRUCTURE

Lysosomes are acidic membrane-bound organelles found within cells, usually around 1 micrometer in length. Lysosomes contain numerous hydrolytic enzymes which catalyse hydrolysis reactions. The membrane surrounding the lysosome is vital to ensure these enzymes do not leak out into the cytoplasm and damage the cell from within. In order to maintain the acidic pH of the lysosome, protons are actively transported into the organelle across the lysosomal membrane.

SYNTHESIS

The lysosome and the enzymes within it are synthesized separately. Lysosomal proteins are formed in the same way as any other protein. The first step is the initialization of mRNA strand production from relevant DNA segments. The mRNA strands proceed to the rough endoplasmic reticulum, where ribosomes construct the hydrolytic enzymes. Importantly, these are tagged with mannose-6-phosphate within the Golgi apparatus to target them to the lysosome. As a result, vesicles containing these enzymes bud off from the Golgi apparatus. Two enzymes are responsible for the attachment of the mannose-6-phosphate tag: N-acetylglucosamine phosphotransferase and N-acetylglucosamine phosphoglycosidase. This vesicle, now in the cytoplasm, then binds with a late endosome which is another acidic, membrane-bound organelle. The late endosome has proton pumps within its membrane that keep its internal environment acidic. The low pH causes dissociation of the protein from the mannose-6-phosphate receptor. This receptor can then be recycled back to the Golgi apparatus. The phosphate group is also removed from the mannose-6-phosphate tag, to prevent the whole protein returning to the Golgi apparatus. The late endosome can eventually mature into a lysosome, after it has received the enzymes from the Golgi apparatus.

FUNCTION

The hydrolytic enzymes contained within the lysosome allow foreign particles to be destroyed. Lysosomes play an important role in phagocytosis. When macrophages phagocytose foreign particles, they contain them within a phagosome. The phagosome will then bind with a lysosome to form a phagolysosome. These enzymes are critical in oxygen-independent killing mechanisms. Lysosomes also help to defend against pathogen entry via endocytosis by degrading pathogens before they reach the cytoplasm.

MITOCHONDRIA (SINGULAR: MITOCHONDRION)

They are double membrane-bound cell organelles with a typical size of 0.75-3 μm². They are found in most mammalian cells, with notable exceptions including mature erythrocytes. Classically referred to as the ‘powerhouse of the cell’, they are the site of the majority of ATP synthesis and are therefore exceptionally important to function both microscopically and macroscopically.

STRUCTURE

Mitochondria have an inner and outer membrane, with an intermembrane space between them. The outer membrane contains proteins known as porins, which allow movement of ions into and out of the mitochondrion. Enzymes involved in the elongation of fatty acids and the oxidation of adrenaline can also be found on the outer membrane. The space within the inner membrane of the mitochondrion is known as the matrix, which contains the enzymes of the Krebs (TCA) and fatty acid cycles, alongside DNA, RNA, ribosomes and calcium granules. The inner membrane contains a variety of enzymes. It contains ATP synthase which generates ATP in the matrix, and transport proteins that regulate the movement of metabolites into and out of the matrix. The inner membrane is arranged into cristae in order to increase the surface area available for energy production via oxidative phosphorylation.

FUNCTION

The mitochondrion is the site of ATP synthesis for the cell. The number of mitochondria found in a cell are therefore a good indicator of the cell’s rate of metabolic activity; cells which are very metabolically active, such as hepatocytes, will have many mitochondria. Mitochondria also have a role to help maintain the intracellular environment. They:

• Store caspases responsible for triggering apoptosis.

• Are able to transiently store calcium contributing to calcium homeostasis.

In brown adipose tissue mitochondria have an alternative function of heat production using the electron transport chain.

DNA AND INHERITANCE

Mitochondria replicate their DNA by a process called binary fission and can use this to make multiple copies in one mitochondrion. Their DNA has maternal lineage which means their DNA is passed from mother to child with little change.

CYTOPLASM

The cytoplasm is a clear substance with a jelly-like consistency. It consists mainly of water but also includes enzymes, salts, organelles such as mitochondria and ribosomes and certain organic molecules. Its principal activities are to dissolve wastes created by the cell and to move materials around inside the cell. It also permits the cells to carry out their specialized functions such as transmitting impulses or storing fats and is therefore vital to effective functioning of the human body. The maintenance of the cell is the responsibility of the various organelles contained in the cytoplasm. The mitochondria in the cytoplasm are the site of cellular respiration which generates energy to enable the cell to function. Within the cytoplasm are a series of channels known as the endoplasmic reticulum. The role of the endoplasmic reticulum is the synthesis, folding, alteration and transport of proteins.

The Cell

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