Human Cell Biology

== Learning goals What is cell biology? It is the study of the human cell structure, function and interactions on a molecular level. This approach helps us understand whole organisms, like us human beings, since we are dependent upon the collective functioning of our cells.

There are three important theories upon which the science of biology is based on. 1- Theory of Evolution. 2- The Cell Theory. 3- The Theory of Equilibrium Thermodynamics.

Since we’re concerned with cell biology now, we should familiarize ourselves with the cell theory which states that all organisms are made of similar units of organization called cells.

However, the present day definition of cell theory includes:

1. All known living things are made of cells.
2. Therefore, cell is the structural and functional unit of all living things.
3. All cells have the same chemical composition.
4. All energy flow (metabolism, biochemistry) of life occurs inside cells.
5. All cells come from pre-existing cells by division.
6. All cells contain hereditary information which is passed from cell to cell during division.

Now these theories help provide a framework to support the ideas in cell biology but are not comprehensive unless we delve deeper and understand more about the cell’s structure and their functions.

The best way to describe a cell is by way of comparison with something familiar. This can be tricky because cells are somewhat unique. The redeeming thing here is once you familiarize yourself with a cell, then it won't matter that a human is made of billions of cells because although they might be different in what they do, they will have the same basic components (like how human beings are; we all have the same basic structure but have different personalities and jobs).

The below are a list of the basic structures inside a cell and have been briefly described but discussed with further detail in subsequent chapters.

1. Plasma membrane: Similar to the skin, it protects the cell from the outside environment. Most importantly, it regulates movements of water, nutrients, and wastes in and out of the cell. It is also called the cell membrane.
2. Cytosol: Semi-fluid medium that is made of water with micromolecules dissolved in it. Parts of the cytosol are made by the cell and partly have defused in from outside. Think of curry soup which was originally water but when mixed with chicken, vegetables and spices and got transformed. Even if we take away the chicken and the other ingredients, the water will no longer be just water, but a concoction of various ingredients dissolved in it. The cytosol along with the organelles of the cell is referred to as the cytoplasm.
3. Nucleus: It is usually at the center of the cell and plays an important role. It contains chromatin (DNA chain) which is the code for synthesizing protein. (What are proteins and why are they important will be discussed in the next chapter. For now, proteins are responsible for most of the functions in the cell). Moreover, nucleolus is concentrated chromatin. Every single cell has all the genetic information (genome) and therefore the ability to produce all the proteins in the body. However, cells usually specialize and only produce a particular set of proteins depending on their location and the requirements. Example; when the nucleus of an undifferentiated cell starts synthesizing muscle protein (because of certain signals it has received), the cell becomes a specialized muscle cell and remains that way.
4. Ribosome: Are proteins on which proteins are made. Similar to an anvil (iron block used to mold metal).
5. Rough Endoplasmic Reticulum (RER): An organelle that looks like an interconnected network of membranes contains many ribosomes (giving it a rough and studded appearance) on which large and complicated proteins can be synthesized.
6. Smooth Endoplasmic Reticulum (SER): Similar structure to an RER but does not contain ribosome and are responsible for making lipids (another micromolecule in which we will talk about in the next chapter).
7. Golgi Apparatus: Also known as Golgi complex, is a group of membranous sacks that are responsible for modifying, storing and transporting products from the endoplasmic reticulum (both proteins and lipids), to other parts and organelles of the cell or and even outside it- similar to how workers in a factory regulate their products and ship them.
8. Mitochondrion: Is the energy power house, the electricity generator (more on it in chapter 5). Many mitochondrion is referred to as mitochondria.
9. Lysosome: Contains enzymes (proteins whose function is to catalyze reactions) that digest nutrient molecules and wastes. It is basically the stomach of the cell.
10. Peroxisome: Also contains enzymes whose main function is to produce and hydrolyze the H2O2 (hydrogen peroxide) of the cell.
11. Cytoskeleton: The mechanical frame-work of the cell, similar to the skeleton of the human body. It is made of different proteins (microtubules, microfilaments and intermediate filaments)
12. Centrioles: Are proteins responsible for synthesizing the spindles (made of microtubules) which pull DNA apart during cell division. It is usually located close to the nucleus.
13. Endosomes: Are transport vesicles made by the inner folding of the plasma membrane (invagination until ultimately a separate internal compartment is created, the process is called endocytosis) to accommodate molecules for transferring to lysosomes or to different parts of the cell.

Again, the entire course on cell biology will be spent discussing the structure and functions of these organelles in detail so you do not need to memorize anything now, just read and understand. Excluded are occasional structures such as cilia, flagella and other secretory vesicles which are sometimes found and will be discussed later when the need arises.

Microscopes are important to visualize cells. The small size of cells makes the use of microscopes necessary; if two objects are close together; they start to look like one object. But if we can distinguish them, then it is said that we’ve resolved them. With normal human vision, the smallest objects that can be resolved is about 200 um (.2 mm in size).

The two most common types of microscopes are light microscopes and electron microscopes.

Light microscopes use light as a source of radiation and have a resolving power of .2 um (200 nm). This is one thousand times better than that of the human eye.

Electron microscopes, on the other hand, use electrons as a source of radiation instead of light. They also have magnets instead of glass lenses to focus an electron beam. The wave-length of an electron beam is far shorter than that of light. And the resulting image resolution is far greater. Also, a fluorescent screen resolution is .5 nm or 400 thousand times better than the human eye. However, in electron microscopes, cells have to be put in a vacuum in order to avoid the molecules in the cell to interact with the other gases in the atmosphere. The problem with this is that water boils in a vacuum at room temperature. Therefore, the cell needs to be dehydrated and killed. In addition, the components of the cell are colorless and need to be stained in order to view them.

Complicated right?

Also, there are two popular types of electron microscopes (EM) that provide different points of view of the cell; Scanning EM which provides a 3-dimensional view of the cell surface or topography and Transmission EM which provides an inside access into the components of a cell and it’s molecules.

Here we discuss the basic components or molecules that the cell is comprised of. This is more a Chemistry 101 lesson than anything else.

There are four classes of organic molecules in a cell:

1. Carbohydrates; As the name indicates, they consist of a Carbon atom (Carbo-) attached to a Hydrogen and an Oxygen atom in the ratio of 2:1, similar to water H2O (-hydrate from hydra in latin meaning water). They have a general chemical formula of (CH2O)n where n is usually any number ranging from 2 onwards. The most popular carbohydrates have n= 3 (triose) or 5 (pentose) or 6 (hexose). Since most carbohydrates are sweet and sugary, sugar nomenclature end with “ose.” They can be classified as single unit sugars which are called monosaccharides (mono means one, saccharide means sugar), or disaccharides (“di” means two therefore two unit sugars joined together), or oligosaccharides (3 to 50 unit sugars joined together) or polysaccharides (“poly” means many and it is above 50 units of sugar joined together). The bond that holds the saccharides together to form carbohydrates is called glycosidic bond and is formed by the loss of a water molecule when two carbohydrates come together and are subsequently joined by the oxygen atom of one of the two saccharides molecules. Carbohydrates are usually used as a food source since sugars are used to convert into energy (a process explained in detail in the Mitochondria section). Example: Glucose (C6H12O6) is a monosaccharide or single unit sugar and is a common source of energy for the body. However, glucose is generally stored as an aggregated giant molecule starch in plants or glycogen in animals. They are polysaccharides or polymers (macromolecules). Actually “poly” means many, and “mer” means molecules therefore it means many molecules. Three important disaccharides are maltose, lactose, and sucrose which are used as fodder to either make the storage macromolecules or to break-down into monosaccharides for converting the sugar into energy. In addition to it’s role as energy storage, carbohydrates are also used in plant cell wall in the form of the polysaccharide cellulose to give the cell structure, and is an important signal receptor on the plasma membrane of cells where the signal will induce the cell to perform specific functions (more in Cell Signalling section). This is done when oligosaccharides linked to proteins on the plasma membrane work as signal receptors or markers for cell recognition and interaction.

2. Lipids; The most distinguishing feature of lipids are the hydrocarbon chain, with a carboxyl group (C=O) at the end. This is the basic structure of lipids and called fatty acid. There are usually between 16-18 carbon atoms in the hydrocarbon chain. The carboxyl end of the fatty acid is highly polar and therefore water soluble (hydrophilic meaning attracted to water). Hydrocarbon chain of the fatty acid is highly non-polar and therefore water insoluble (hydrophobic, which means scared of water). When fatty acids interact with water, the soluble carboxyl end dissolves and forms a layer with water, while the hydrocarbon tale remains outside the water surface. This quality is important in forming the bio membrane of cells which will become clearer in the biomembrane section. Also, another quality to remember is when all carbon atoms of the hydrocarbon chain in the fatty acid are joined by a single bond, the compound is said to be saturated, this means that every carbon atom has hydrogen atom on both sides. In unsaturated fatty acid, one or more carbon atoms form a double bond with another carbon atom. Therefore, it will not be able to hold a hydrogen atom and therefore said to be unsaturated. As you can observe from the first diagram, there are two hydrocarbon tails, one is saturated and the other unsaturated and where the carbon atom forms a double bond, there can be seen a kink in the tail. Usually fatty acids are stored in the form of triglycerides- glycerol molecule + 3 fatty-acid tails. A glycerol molecule plus a fatty-acid tail is a glyceride molecule. The diagram shows us a diglyceride consisting of two fatty-acids linked to a glycerol molecule. Triglycerides are insoluble in water and therefore group as fat droplets in the cytoplasm of the cell. When required, they can be broken down for use as energy. Lipids provide an important form of energy storage, since they give more than twice as much energy as carbohydrates of the same mass. Also, as previously stated, they are the major components of cell membranes. Lastly, they play important roles in cell signaling. Example: steroid hormones, such as estrogen and testosterone are made of cholesterol and used in processing food and building nerve cells, apart from other metabolic functions.

3. Proteins; They are structurally important to the cell since they are the basic components of which the cytoskeleton is made, and functionally important since it is responsible for catalyzing reactions in the form of enzymes, have mobility functions, act as signal molecules for the cell and are part of a complex to form receptors for those signals and pretty much most other complicated functions. Due to these reasons, they are structurally complex as well. Proteins are large polymers of amino acids joined together through peptide bonds to form polypeptides or in other words proteins. This is unclear unless you know what each bolded syllable is. First, Amino Acids. Each amino acid consists of a central carbon atom bonded to a; i- Carboxylic-acid group (COOH); A carbon atom double-bonded to an oxygen atom and single bonded to a hydroxyl group (O-H). ii- Amino group (NH2); This is simply a nitrogen atom single bonded to two hydrogen atoms. iii- Hydrogen atom; iv- A distinctive side-chain that is unique to each type of amino acid, usually referred to as the “R” group. Thus, amino acids differ only in their side chains. Amino acids get their name because of the amino group and the carboxylic acid group.

When two amino acids come close together, the hydroxyl group (OH) of the carboxylic-acid, which is polar, attracts a hydrogen atom of the amino group of the other amino acid and in the process, forms and releases a water molecule. This leads to the formation of a peptide bond which is a covalent bond between the carbon of the carboxylic-acid group of the first amino acid and the nitrogen of the amino group of the second amino acid. When many amino acids are linked together through peptide bonds, they form a polypeptide chain (or proteins). Proteins are structurally complex. If you look at one, you can only see chaos. This is due to the fact that when amino acids begin to form peptide bonds with one another, they do not line up into a straight linear structure, rather, they begin to spiral and coil due to the interaction of their side chains with one another forming various types of (mostly) hydrogen and (sometimes) sulphur bonds. So, in order to understand them, we theoretically unwind them and classify their structure under four different sections; i- Primary Structure; the direct peptide links between successive amino acids in a chain noting what the exact sequence of amino acids are that make up the protein.

ii- Secondary Structure; when the amino acids grow in number in the polypeptide chain, they begin to coil and either form an alpha helix (shown in diagram) or a beta-pleated sheet due to the indirect hydrogen links between the R-groups of the different amino acids. Here we discuss the amino acids which are forming those hydrogen links, usually four or five amino acids apart.

iii- Tertiary Structure; the spiral will itself coil and continue to spiral, thus the R-groups of amino acids from different locations (20 or 30 amino acids apart) in the chain will begin to interact and form hydrogen bonds.

iv- Quaternary Structure; here, two or more polypeptide chains will come close and interact with each other forming a dimer (two molecules), trimer (three molecules), tetramer (four molecules) and so on.