Cells

In the past, a good deal of physiology was developed by concentrating on the cell environment: the fluid that makes up blood plasma and the fluid that surrounds the cells. Human cells survive only in highly specialised environments where the relative proportions of minerals, water, nutrients and other constituents remain within narrow limits. Observations can then be focused on how the body's organs protect the cellular environment from change. Modern technology has allowed access to the interior of living cells. Processes occurring within the cell are now observable and measurable. It is now no longer a case of being on the outside looking in but actually being inside. Cells come in different sizes, shapes and internal structures. Liver cells differ from brain cells which differ from blood cells. All cells contain "mini-organs" called organelles with each specialised to perform a specific function. Those commonly appearing in most cells include the following structures and organelles.

Cell (plasma) membrane

The outer boundary of the cell consists of fatty (lipid) molecules (hydrophobic) in which protein is embedded. Some of these proteins provide pathways for transport and regulate the flow of materials into and out of the cell. Other proteins serve as receptors for chemical signals coming from other cells.

Nucleus

The most prominent celullar organelle and contains genetic material: genes, DNA and chromosomes. This information is stored in genes and so directs cell life and reproduction. It contains the nucleolus which is a region densely packed with chromosomes together with some protein and RNA strands. The nucleus initiates the formation of ribosomes, structures necessary for protein synthesis. The nucleus is surrounded by a double membrane that is riddled with pores involved in transporting materials between the nucleus and the rest of the cell.

Cytoplasm

The cytoplasm occupies the space between the nucleus and plasma membrane and contains membrane bound organelles (the ribosomes for synthesizing cytoplasmic proteins) and a complex network of filaments and tubules called the cytoskeleton. The cytosol is the fluid portion of the cytoplasm that exists between these structures and contains many enzymes (proteins).

Mitochondria

The "power houses" of cells are sites where chemical energy is contained within nutrients, but trapped and stored through the formation of ATP molecules. This carries out cellular work supplying energy required for movement, secretion and synthesis of complex structures.

Endoplasmic reticulum

The ER is a network of tubes and flattened sacs (formed by membranes), that is distributed throughout the cytoplasm. Rough ER has a granular appearance caused by the ribosome particles. These are the sites for protein synthesis that is destined for organelles and cell membrane components or secretion to the cell exterior (hormones). Smooth ER lacks the attached ribosomes and is commonly involved in lipid metabolism, but can serve in detoxification of drugs and deactivation of steroid hormones. In smooth muscle cells, the sarcoplasmic reticulum (a special form of ER) sequesters the large amounts of calcium used to trigger muscular contraction.

Golgi apparatus

The Golgi apparatus consists of sets of smooth membranes that form flattened, fluid-filled sacs and are stacked like pancakes. They are involved in modifying, sorting and packaging proteins for delivery to other organelles. Numerous membrane-bound vesicles are frequently found in the Golgi apparatus that probably carry material between the Golgi apparatus and the other organelles of the cell (receiving protein-laden vesicles from rough ER or delivering other vesicles to the plasma membrane).

Endo- and exocytotic vesicles

Membrane-enclosed vesicles travelling from (and to) the plasma membrane are important carriers for protein delivery into (or out of) the cell. Exocytosis (secretion) involves an actual fusion of vesicle membrane with the plasma membrane, enabling vesicle contents to be expelled (secreted) outside the cell. In endocytosis (pinocytosis, phagocytosis) the reverse occurs and the plasma membrane infolds and engulfs extracellular material. A membrane-bound vesicle (containing the material and surrounding fluid) buds off and is incorporated into the cell.

Lysosomes

The lysosomes are membrane-bound vesicles and contain enzymes capable of digesting natural particles, damaged organelles and bacteria brought into the cell via endocytosis.

Cytoskeleton

The cytoskeleton consists of arrays of protein filaments that form networks within the cytosol giving the cell its shape. The filaments provide the basis for movement of both the entire cell and its components (organelles). They are the "bones and muscles" of the cell. Cytoskeleton appears to be organized from a region near the nucleus containing a pair of centrioles (particularly important during cell division). There are three major types of cytoskeleton filament:

• Microtubules (25nm)
• Actin filaments (7nm)
• Intermediate filaments (10nm)

Diameters in nanometres (nm).

Epithelial cells (epithelium) adhere to one another often forming layered sheets with very little space in between and are found at surfaces that cover the body or that line the walls of tubular or hollow structures: skin, linings of lungs, gastrointestinal tract, bladder and blood vessels. The sheets often form boundaries between different body compartments where they regulate exchange of molecules between those compartments. Virtually all substances which enter or leave the body must cross at least one epithelial layer. The small intestine forms a hollow cylinder the interior lining of which is populated by several types of epithelial cells. Some secrete digestive enzymes, some absorb nutrients and still others secrete a protective mucus. The epithelial cells are called upon to transport materials in one direction only: either from blood vessels embedded within the intestinal walls to the hollow interior (lumen) of the cylinder in the case of secretion or from lumen to blood in the case of absorption. The cell must have a "sense of direction" to know the difference between the lumen side and the blood side. This asymmetry in function is reflected in an asymmetrical structure and is revealed by both the cell shape and organelle position and is probably established and maintained by an elaborate cytoskeleton. There are striking differences in the plasma membranes located at various sides of the cell. The apical (at the apex) or mucosal surface faces the outside environment or the lumen of a particular organ. The basal surface is on the opposite side, the side that lies closest to the blood vessel. The lateral sides face neighbouring epithelial cells. Each of these membrane surfaces contains different proteins and structures required for normal function.

The lateral surfaces of epithelial cells must adhere to one another to maintain their sheet-like structure and to provide tight seals between adjacent cells so that fluids and other substances cannot leak between them. If substances do move across the epithelial layer it is generally because they are selectively recognised and transported by the cells themselves. Discrete (distinct) structures called desmosomes provide a major source of this adhesion. They lie close to or within the membrane and bind the cells together where they come into contact with each other. Other specialised contact sites (tight junctions) are used to plug potential leaks, still others (gap junctions) are used for cell-to-cell communication. Collectively, these contact sites are called cell junctions. Desmosomes are regions of tight adhesion between cells that give the tissue structural integrity. They are concentrated in tissues like skin, which are subjected to mechanical stress. At a desmosome, there is a small extracellular space between the two cell membranes that is filled with a fine filamentous material that probably cements the two cells together. There are two types of desmosomes - belt and spot, respectively continuous zones of attachment that encircle the cell and more-local attachments to small regions of contact like "spot welds". Tight junctions form very close contacts between neighbouring cells, leaving virtually no space between them. These junctions extend around the entire circumference of the cell providing a tight seal that prevents leakage of fluids and materials. Gap junctions are specialised between adjacent cells and consist of an array of six cylindrical protein subunits that spans the plasma membrane and reaches out a short distance into the extracellular space.

The subunits are bunched together with their long axis parallel to one another in a manner that forms an open space or channel about 1.5nm wide running the entire length of the array. These channels act as pores that tunnel through the membrane, but the tunnels do not empty into the extracellular space. Instead, each array attaches to a similar array in an adjacent cell forming a tunnel of double the length with the entrance in one cell and the exit in the adjacent cell. These tunnels are wide enough to allow small solutes and common ions to pass between them. The junctions provide for the passage of electrical and chemical signals between the cells, allowing them to function in unison. Under certain circumstances, the central channel closes isolating that cell from the others. The most common type of cell junction (gap junctions) is particularly important in co-ordinating the heart, smooth muscle and epithelial cell activities. Microvilli are small finger-like projections found on the apical surface of epithelial cells They are most abundant in tissues that primarily transport molecules across the epithelial sheet. Microvilli are advantageous because they greatly increase the surface area available for transport (by a factor of 25 in the intestine). Actin filaments anchored at their base in the terminal web of fibres running the entire length of the microvilli are believed to provide support for their upright position. Cilia are very long projections from the apical surface that are involved in transporting material along the epithelial surface rather than through it. They are abundant in the respiratory tract, oviducts and uterus. They function with "beating" (whip-like) movements that mechanically propel fluids and particles on the cellular surface in the direction of a rapid forward stroke. An array of microtubules that runs the length of each cilium mediates these motions.

Structure of cell membranes

Cell membranes are ubiquitous and they define the boundaries of cells and the subcellular organelle. They transmit signals across these boundaries, contain cascades of enzymes that are essential for metabolism and regulate which substances enter and which leave. All cell membranes share a common primitive structure although they may have different components. They are composed of proteins floating in a fluid bilayer (two layers back to back) of lipid. The forces holding the membrane together appears to arise from the interaction of membranes with water and water with itself. Water is a polar molecule having a positive and a negative charge distribution but is overall a neutral species. It forms aggregates of several molecules in association weakly held by H-bonds. Water also interacts with other polar molecules but not with non-polar molecules. These are excluded from the water phase and are insoluble. Hydrophilicity is water-seeking but hydrophobicity is water-repelling. Most membrane lipids are phospholipids and have a dual structure. One end is hydrophilic (polar head) and is attracted to water. The other end is the hydrophobic (non-polar) tail and is ejected from water. When phospholipids are mixed with water, forces tend to align the molecules with the head attracted to water and the tail repelled. Micelles or bilayers are formed. The same principles apply to cell membrane proteins. Proteins do not have an obvious head and tail but are folded so that hydrophobic parts are out of the water phase, embedded in the hydrophobic part of the membrane (more non-polar), while the polar parts are anchored in the water.

Specific proteins embedded in the membrane perform specific functions. Some are involved with transport of materials into or out of the cell while others act as receptors for hormones. Others catalyze specific chemical reactions and still others act as links between cells or act as "anchors" for structural elements inside the cell. Some proteins traverse the entire cell membrane, but others are confined to a single side. Proteins exposed to the external surface of the cell membrane frequently have carbohydrate side chains attached and are called glycoproteins. Those that span the membrane is exposed to both surfaces and are often involved with the transport of materials into and out of the cell. Some appear to form clusters of perhaps two or four molecules in the membrane and some are believed to fold in ways that confine polar parts to an interior core that runs through the centre of the molecule or through the centre of the cluster.

This would provide a channel for small polar molecules, particularly water and ions, to move through the membrane. Some of these channels may contain "gates" or "filters" or some other device to regulate transport. Forces generate movement and concentration gradients allow diffusion, while pressure gradients cause bulk flow. Electrical (voltage) gradients or membrane potentials, drive the flow of ions (ionic current). Water flows to the side of the more concentrated solute by osmosis.

Diffusion

Under most circumstances, the diffusion of different substances is independent of each other. Solutes diffuse down their concentration gradients from the more concentrated to the less concentrated region arising because molecules are always moving at random. The time required for diffusion over small distances such as cell size takes only a fraction of a second, but larger distances take much longer times. If oxygen were to move by diffusion it would take about 53 days to move 10cm. However, such movement is by bulk flow through the circulating blood. It diffuses the short distance through the wall of the blood vessel (capillary) into the tissue and to any cell in the vicinity. The process is over in seconds.

Bulk flow

Unlike diffusion, bulk flow involves whole mass movement (fluid and many dissolved solutes). The "push" or pressure is the force exerted per unit area and fluid flows down pressure gradients from high to lower pressure.

Osmosis

The movement of solute through a semi-permeable membrane is known as osmosis. It is permeable to the solvent (water), but not permeable to the solute (dissolved component). Water will flow from a region of low solute concentration to higher solute concentration so that there is a balancing up of the concentration by diluting the higher concentration side of the membrane. This flow is called osmosis. The more concentrated the solution the higher the osmotic pressure or the movement is essentially more rapid. This pressure is solute dependent. Osmosis involves bulk flow. Consider a solution of protein on one side of a semi-permeable membrane but an equal concentration of a sugar on either side. The membrane will allow sugar molecules to pass but restrain the larger protein molecules. Water will pass from the lower concentration side to the higher (protein solution) side, but take with it the sugar solute molecules. The overall (total) solute concentrations are different - on the one side is only sugar solution but the other is a solution of the same solute concentration of sugar, but additionally a fixed amount of protein.

Osmotic flow takes place in bulk. The solvent (water) drags all solutes along with it except those that are restrained by the membrane (ionic current). A small difference in the electrical current on two membrane surfaces causes ionic movement. Unlike charges attract, like charges repel so that when positive and negative charges are separated, they tend to move back together. The energy associated with this attraction or repulsion is the voltage. Positive ions move down voltage gradients and negative ions move up voltage gradients. Concentration, pressure, osmotic and voltage gradients are all (free) energy gradients and are forces that generate movement.