The cell membrane

As can be seen in Fig. 1.2, the various structures of the cell are contained within a cell membrane (also known as the plasma membrane). This cell membrane is a semi‐permeable biological membrane separating the interior of the cell from the outside environment, and protecting the cell from its surrounding environment. It is semi‐permeable because it allows only certain substances to pass through it for the benefit of the cell itself. For example, it is selectively permeable to certain ions and molecules (Alberts et al., 2014). Inside the cells are the cytoplasm and the organelles, which include, for example, the lysosomes, mitochondria, and the nucleus of the cell.

The cell membrane, which can vary in thickness from 7.5 nm (nanometres) to 10 nm (Vickers, 2009) is made up of a self‐sealing double layer (bilayer) of phospholipid molecules with protein molecules interspersed amongst them (Fig. 1.3). A phospholipid molecule consists of a polar ‘head’, which is hydrophilic (mixes with water), and a tail that is made up of non‐polar fatty acids, which are hydrophobic (repel water). In the bilayer of the cell membrane, all the heads of each phospholipid molecule are situated on the outer and inner surfaces of the cell facing outwards, whilst the tails point into the cell membrane; it is this central part of the cell membrane consisting of hydrophobic tails that makes the cell impermeable to water‐soluble molecules (Marieb, 2014). In addition to the phospholipid molecules, the cell membrane contains a variety of molecules, mainly proteins and lipids, and these are involved in many different cellular functions, such as communication and transport. The proteins inserted within the cell membrane are known as plasma member proteins (PMPs), which can be either integral or peripheral. Integral PMPs are embedded amongst the phospholipid tails whilst others completely penetrate the cell membrane. Some of these integral PMPs form channels for the transportation of materials into and out of the cell, others bind to carbohydrates and form receptor sites (e.g., attaching bacteria to the cell so they can be destroyed). Other examples of integral PMPs include those that transfer potassium ions in and out of cells, receptors for insulin, and types of neurotransmitters (Vickers, 2015). On the other hand, peripheral PMPs bind loosely to the membrane surface, and so can be easily separated from it. The reversible attachment of proteins to cell membranes has been shown to regulate cell signalling, as well as acting as enzymes to catalyse cellular reactions through a variety of mechanisms (Cafiso, 2005).

Functions of the cell membrane

Briefly, the two major physiological functions of the cell membrane are endocytosis and exocytosis. These are both concerned with the transport of fluids and other essential particulates and waste matter into and out of the cell.

• Endocytosis is the passing of fluids and small particles into the cell. There are three types of endocytosis, namely:
  
  
  
  • Phagocytosis – the ingestion of large particulates, such as microbial cells
    
  • Pinocytosis – the ingestion of small particulates and fluids
    
  • Receptor‐mediated – involving large particulates, such as protein. It is also highly selective as to which particulates are taken up.

Endocytosis involves part of the cell membrane being drawn into the cell interior, along with particulates or fluid, in order to facilitate their ingestion. This part of the membrane is then ‘pinched off’ to form a vesicle within the cell. At the same time, the cell membrane reseals itself. Once inside the cell, the fate of this vesicle depends upon the type of endocytosis involved and the material that is contained within the cell membrane surrounding it. In some cases, the vesicle may ultimately fuse with a lysosome (an organelle), following which the ingested material can be processed. Endocytosis is also the means by which many simple organisms – such as amoeba – obtain their nutrients.

The cell membrane and transport

Selective permeability, as mentioned in the previous section, is very important to the process of transporting materials into and out of the cell, allowing certain materials to pass through the membrane, whilst preventing others that could harm the cell. This process depends upon the hydrophobicity of some of its molecules (as mentioned earlier). Because the phospholipid molecule tails are composed of hydrophobic fatty acid chains, it is difficult for hydrophilic (water‐soluble) molecules to penetrate the membrane. Hence it forms an effective barrier for these types of molecules, which can only be penetrated by means of specific transport systems that control what can enter or leave the cell. For example, the membrane controls the process of metabolism by restricting the flow of glucose and other water‐soluble metabolites into and out of cells – as well as between subcellular compartments. In addition, the cell stores energy in the form of transmembrane ion gradients by allowing high concentrations of particular ions to accumulate on one side of the membrane. Ions can pass through the membrane from inside the cell to the outside – or vice versa – so that there are more supplies of these ions just outside the cell or inside it. The membrane controls the speed/rate at which these ions pass through the membrane. The controlled release of such ions on the gradients can be used for:

• extracting nutrients from the fluids around the cells
  
• passing electrical messages (nerve excitability)
  
• controlling the volume of the cell.

Cell membrane permeability

There are four factors involved in the degree of permeability of a cell membrane, namely:

1. The size of molecules – large molecules cannot pass through the integral membrane proteins, whilst small molecules (e.g., water, amino acids) can.
   
2. Solubility in lipids (fats) – substances that easily dissolve in lipids (e.g., oxygen, carbon dioxide, steroid hormones) can pass through the membrane more easily than non‐lipid soluble substances can.
   
3. If an ion has an electrical charge that is the opposite of that found in the membrane, then it is attracted to the membrane and so can more easily pass through it.
   
4. Carrier integral proteins can bind to substances and carry them across the membrane, regardless of the three processes above, i.e., size, ability to dissolve in lipids, or membrane electrical charge.

Movement of substances across the membrane

There are two ways for this to occur, namely, passive and active.

Passive processes

A passive process is one in which the substances move under their own volition down a concentration gradient from an area of high concentration to an area of lower concentration. In this process, the cell expends little energy on the process (like rolling down a hill).

There are four types of passive transport processes, namely:

• diffusion
  
• facilitated diffusion
  
• osmosis
  
• filtration.

Diffusion is the most common form of passive transport. A substance in an area of higher concentration moves to an area of lower concentration (Colbert et al., 2012). The difference seen between areas of different concentrations is known as the concentration gradient. This particular passive transport process is essential for respiration. It is through diffusion that oxygen is transported from the lungs to the blood and carbon dioxide from the blood into the lungs.

Although similar to diffusion, facilitated diffusion differs from it by the use of a substance (a facilitator) to help in the process (see Fig. 1.4). As an example, glucose is moved using this process. To be able to pass through a membrane, glucose needs to attach itself to a carrier/transport protein (McCance & Huether, 2014).

Osmosis is the process by which water travels through a selectively permeable membrane so that concentrations of a solute (a substance that is soluble in water) are equal on both sides of the membrane. This gives rise to osmotic pressure. The higher the concentration of the solute on one side of the membrane, the higher the osmotic pressure available for the movement of water (Colbert et al., 2012).

If osmotic pressure rises too much, then it can cause damage to the cell membrane, so the body attempts to ensure that there is always a reasonable constant pressure between the cell’s internal and external environments. We can see the possible damage if, for example, a red blood cell is placed in a low concentrated solute, then it will undergo haemolysis. On the other hand, if it is placed in a highly concentrated solute, the result will be a crenulated cell. If the red blood cell is placed in a solution with a relatively constant osmotic pressure, it will not be affected because the net movement of water in and out of the red blood cell is minimal.

Filtration is similar to osmosis, with the exception that physical pressure is used in order to push water and solutes across a cell membrane. This is seen in renal filtration, where the heart beating exerts pressure as it pushes blood into the kidneys, where filtration of the blood can then take place to remove any impurities (Colbert et al., 2012).

Active processes

Active processes are:

• active transport pumps
  
• endocytosis
  
• exocytosis.

An active process is one in which substances move against a concentration gradient from an area of lower to higher concentration. In order for this to happen, the cell must expend energy, which is released by the splitting of adenosine triphosphate (ATP) into adenosine diphosphate (ADP) and phosphate.

ATP is a compound of a base, a sugar and three phosphate groups (triphosphate), and is held together by phosphate bonds, which release a high level of energy when they are broken. Once one of the phosphate bonds is broken and phosphate has been released, that compound then becomes ADP. The ‘spare’ phosphate will then join another ADP group, so forming ATP (with energy stored in the phosphate bond). This process is continually recurring within the body.

Active transport pumps need energy to be able to function. This energy occurs as a result of the reaction mentioned earlier. It is necessary when the body is attempting to move an area that already has a high concentration of that substance. The higher the concentration already present, the more energy is required to move further molecules of that substance into that area. Fig. 1.5 demonstrates the effect of solute concentration on a red blood cell.

The organelles

These are rather like small ‘organs’ within the cells. The following sections give a brief overview of the many cell organelles and their functions.

Cytoplasm

Although, not strictly speaking, an organelle, the cytoplasm is a very important and integral part of the cell interior. Cytoplasm is ground substance (a ‘matrix’) in which various cellular components are found. It forms part of the protoplasm of the cell (protoplasm is the collective name for everything within a cell). Cytoplasm is a thick, semi‐transparent, elastic fluid containing suspended particles along with the cytoskeleton (the cell framework). The cytoskeleton provides support and shape to the cell and is involved in the movement of structures within the cytoplasm – for example, phagocytic cells. Chemically, cytoplasm is made up of 75–90% water along with solid compounds, particularly carbohydrates, lipids and inorganic substances.

The nucleus (see Fig. 1.2)

The cell nucleus is the control centre of a family of cells known as eukaryotes. Eukaryotic cells are found in animals (including humans) and plants. These cells include the prokaryotic cells that are very typical of bacteria – these cells tend to be less complex and often smaller than eukaryotic cells. However, not all human cells have a nucleus. A good example is the red blood cell. The mature red blood cell has lost its nucleus and consequently is concave in shape because it has ‘collapsed in’ on itself. There are also some human cells (some muscle fibre cells) that have more than one nucleus (see Fig. 1.1).

Cell reproduction

In order for the body to grow and also for the replacement of body cells that die or are damaged, our cells must be able to reproduce themselves. In order that the genetic information contained in the cells of the body is not lost, this must be achieved accurately.

As mentioned earlier, in humans there are a total of 23 pairs of chromosomes in each human cell that contains a nucleus. Cells reproduce by means of two processes: mitosis and meiosis, with most cells being reproduced by mitosis, whilst meiosis is restricted to the gender cells, namely the spermatozoa and the ova.

The majority of the cells that are reproduced by mitosis are exact replicas of the parent cells, and contain the full complement of 23 pairs of chromosomes, whilst those cells reproduced by meiosis are totally different in that they only contain one of each of the 23 chromosomes.

To ensure that all the genetic information is passed on accurately, in mitosis, the chromosomes reproduce themselves and then the cell divides into two, ensuring that one pair of each of the chromosomes is found in each new cell. Meiosis, however, is different in that, although initially the process is the same as in mitosis, the cells then undergo other procedures so that the end product is cells with only one copy of each chromosome. This is essential for the reproduction, not of cells, but of humans, as explained briefly in the following paragraph.

During the reproduction of humans, an egg (ovum) is penetrated by a sperm (spermatozoa), which then releases its chromosomes containing DNA which will then combine with the DNA of the egg. Because these two cells (ovum and spermatozoa) only contain one copy of each chromosome rather than the two carried by all other cells of the body, the ovum will only have two copies of each chromosome containing DNA. If the process of meiosis did not take place and the egg and sperm were like all the other cells in the body and had the normal two copies of each chromosome, then the resulting embryo would end up with four copies of each chromosome. If this process was repeated, then the next generation would end up with eight copies of each chromosome, and the following generation with 16 copies …, and so on. This is obviously not practical, which is why the ova and spermatozoa undergo meiosis to ensure that only two copies of the chromosomes are present in each succeeding generation. This will be explored more fully in Chapter 2.

Other organelles

All cells contain many organelles, and these are discussed in the following sections.

Endoplasmic reticulum

The endoplasmic reticulum (ER) consists of membranes that form a series of channels known as cisternae (see Fig. 1.6). These divide the cytoplasm into compartments. There are two types of cisternae:

1. granular ER (rough), which is associated with ribosomes (see Chapter 2)
   
2. agranular ER (smooth), which is free of ribosomes.

Ribosomes include tiny particles of RNA – these are formed in the cell nuclei and are associated with the synthesis of proteins need by the cell.

• The membranes of the ER contain many enzymes that speed up chemical reactions within the cells.
  
• ER consists of a series of channels (cisternae), which are concerned with the transport of materials – particularly proteins.
  
• ER contains a number of enzymes that are important for cell metabolism – such as digestive enzymes, enzymes that are involved in the synthesis (production) of steroids, and enzymes that lead to the removal of toxic substances from the cell (McCance & Huether, 2014).
  
• The alteration/addition of proteins exported from the cell also occurs in the cisternae.
  
• ER is also present in liver cells, where it has a role to play in drug detoxification.
  
• Granular ER is particularly found in cells that actively synthesise and export proteins.
  
• Agranular ER is found in steroid hormone‐secreting cells, such as the cells of the adrenal cortex or, in males, the testes.

Golgi complex (Fig. 1.2)

The Golgi complex (also known a Golgi apparatus) is a collection of membranous tubes and elongated sacs. These are actually flattened cisternae that are stacked together. The Golgi complex has two major roles:

1. Helping to concentrate and package some of the substances that are made in the cell itself, for example, lysozymal enzymes.
   
2. Helping with the assembly of substances for secretion outside of the cell. Secretory cells (such as those found in the mucus membrane) have many Golgi stacks, whilst non‐secretory cells have few Golgi stacks per cell.

Proteins for export from the cell are, first of all, synthesised on the ribosomes. They then travel through the ER to the Golgi vesicles (a vesicle is a fluid‐filled sac). The vesicles leaving the Golgi complex then fuse with the cell membrane by the process of exocytosis. This allows the contents of the vesicles to be exported out of the cell.

In addition, the Golgi complex is itself involved in the formation of glycoproteins.

Lysosomes (Fig. 1.2)

Lysosomes are organelles that are bound to the cell membrane and they contain a variety of enzymes. They have a number of functions:

• They are responsible for the digestion of material (e.g., pathogenic organisms) taken up by the process of endocytosis.
  
• They can break down components within the cell when they are not needed. For example, during the development of a human embryo, the fingers and toes of the embryo are webbed and the lysosomal enzymes remove the cells making up the webbing from between the digits.
  
• After the baby’s birth, the uterus (which can weigh around 2 kg at full term) is invaded by phagocytic cells that are rich in lysosomes. These then reduce the uterus to its non‐pregnant weight of approximately 50 g within about 9 days.
  
• In normal cells, some of the synthesised proteins may be faulty, and so, consequently, it is the lysosomes that are responsible for their removal and destruction.

It is crucially important that lysosomes do not rupture and release their contents inside living cells that we need to function, otherwise the lysosomal enzymes would start to digest and destroy the cell that is needed. If this occurs, the results can be seen in certain degenerative diseases, such as rheumatoid arthritis. The rupturing and breaking down of lysosomes from macrophages causing the release of lysosomal enzymes may be a significant factor in the attacking and destruction of essential living cells and tissues.

Lysosomes also contribute to the production of hormones, such as thyroxine. Thyroxine is a hormone that affects a wide range of physiological activities, such as the rate of metabolism throughout the body.

Peroxisomes (Fig. 1.2)

Peroxisomes are organelles that are similar in structure to lysosomes. However, they are much smaller. These organelles are particularly abundant in the cells of the liver, and they contain several enzymes that are toxic to cells of the body.

The role of peroxisomes in cells appears to be one of detoxification of harmful substances – such as alcohol and formaldehyde – within the cell. Importantly, they also neutralise dangerous free radicals. Free radicals are highly reactive chemicals that contain electrons that have not been ‘paired off’, and so are ‘free’ to disrupt the structure of molecules (Marieb, 2014).

Mitochondria (Fig. 1.2)

Mitochondria (mitochondrion, singular) are often thought of as the ‘power houses’ of the cell because they generate most of the cell’s supply of adenosine triphosphate (ATP), used as a source of energy. The mitochondria are often found concentrated in regions of the cell associated with intense metabolic activity.

Anatomically, mitochondria consist of two membranes (an inner and an outer) and an intermembrane space.

The inner membrane has many folds (cristae) that increase the surface area available for chemical reactions to occur, such as the production of ATP (adenosine triphosphate – a coenzyme used as an energy carrier in the cells of all known organisms, which is responsible for the process in which energy is moved throughout the cell). This process is collectively known as internal respiration. The inner membrane is of the same thickness as the outer membrane and is responsible for oxidative phosphorylation.

The mitochondrial matrix is the name given to the space that is surrounded by the inner membrane. It contains enzymes of the tricarboxylic acid (TCA) cycle, as well as those enzymes involved in fatty acid oxidation. About two‐thirds of the total protein is found in mitochondria, and, with the inner membrane, they play an important role in the production of ATP, and contain a very concentrated mixture of hundreds of enzymes.

The intermembrane space: Because the outer membrane is freely permeable to small molecules, there is a high concentration of small molecules, such as ions and sugars. However, larger molecules cannot enter this space unless they possess a specific signalling code that allows them to be able to pass through the outer membrane.

The outer mitochondrial membrane encloses the entire organelle. It contains large numbers of integral membrane proteins, known as porins, which form channels in the membrane to allow small molecules to diffuse easily from outside the mitochondria to the intermembrane space, and vice versa. Any disruption of the outer membrane allows proteins in the intermembrane space to leak into the intercellular fluid in the cell (cytosol), leading to certain cell death.

By using ATP, the mitochondria are able to generate the energy needed by the cell for it to be able to function by converting the chemical energy contained in molecules of food. The production of ATP, therefore, requires the breakdown of food molecules, and it occurs in several stages, each requiring the appropriate enzyme. Note that an enzyme is a protein that can initiate and speed up a chemical reaction (it acts as a catalyst). The enzymes in the mitochondria are stored in the membranes in the required order so that the chemical reactions occur in the correct sequence. This mechanism is very important, as it would be disastrous if the chemical reactions occurred out of sequence.

Mitochondria are self‐replicating, in that, although most of a cell’s DNA is contained in the cell nucleus (see Chapter 2), the mitochondrion has its own independent genetic organisation that is really quite similar to that of bacteria. DNA that is incorporated into the mitochondrial structure controls its own replication system.

The cytoskeleton

The cytoskeleton is a lattice‐like collection of fibres and fine tubes and these are found in the cytoplasm of the cell. It is involved with the cell’s ability to maintain and alter its shape as required (see Fig. 1.7).

There are three components that make up the cytoskeleton:

• microfilaments
  
• microtubules
  
• intermediate filaments.