Cells intro

First, a fun science meme

Ran across this meme and thought might be both funny and educational.


All living things are made of cells

Why? Because I said so. Well, not because
I said so. This is something called the “cell theory of life” and it builds into our definition of life the requirement for cells. There are a lot of ways in which this makes sense. However, there are many biological entities, most notably, viruses, which are not cellular and at least fulfill many of the other requirements for being alive.
There is a pretty
good interactive site here.


of a cell
We looked at diagrams of “generic” animal and plant cells (by generic, I really mean cells that don’t look like any real cells.
I want you to know the names and general descriptions of the major organelles.

  1. Nucleus: large structure that houses the chromosomes (DNA). All RNA for the cell is made there, using the DNA as a template. It is encased by a double membrane. That is, two complete lipid bilayers. There are pores, or holes, for the transport of stuff out. These are cleverly named "nuclear pores."
  2. Nucleolus: dense structure in the nucleus. It is the site of ribosome assembly. Ribosomes are then transported to the cytoplasm through the pores. Some scary numbers: a single mammalian cell may have 10,000,000 ribosomes and about 10,000,000,000 protein molecules (numbers form British Society for Cell Biology).
  3. Rough endoplasmic reticulum: Membrane stack near the nucleus. Site of synthesis of proteins that either end up in membranes or are secreted out of the cell (secreted merely means transported out of the cell). They are “rough” because they are dotted with ribosomes. Note: ribosomes are not ALL here. Most make proteins that stay inside the cell and work in the cytoplasm, not the ER membrane.
  4. Smooth endoplasmic reticulum (Lacks ribosomes): Has many varied functions depending on cells. Is the site of phospholipid synthesis, steroid synthesis and used to manage calcium ion concentrations in cells that really use a lot of that (such as muscle cells).
  5. Golgi apparatus: Stacks of membranes that are between the rough ER and the plasma membrane. Proteins are transported from the ER to the Golgi in spheres of membrane called “vesicles.” In the Golgi, proteins are processed (usually meaning sugar molecules are added to specific amino acid residues).
  6. Plasma membrane or cell membrane: the lipid bilayer that keeps the outside out and the inside in. It also has many proteins in it, which may function, for example, as channels allowing transport of nutrients, or allow cells to grab other surfaces or detect the presence of various molecules.
  7. Lysosomes: Spherical membranes that derive from the plasma membrane. Imagine them as pinching off from the membrane and taking in with the membrane any proteins in the area that pinches off. They are sites for “recycling” components of proteins.
  8. All together, numbers 3-6 (actually starting at the nuclear envelope) make up sort of one continuous super-organelle comprising a system of membranes. If I were to make radioactive lipids and put them in the cell, so I could detect the radiation where ever it was, I would find the “hot” lipids show up first in the smooth ER next the nuclear nuclear envelope, and then later would be detected in each of the other places as time passed.
  9. Mitochondria: these are the sites in which the high energy molecules from your food are broken down to low energy products (water and CO2) and the released free energy is captured in other high-energy molecules such as ATP, used to help run many reactions in your body. Mitochondria have their own chromosome (circular, like bacteria), their own ribosomes and their own tRNA. The function of all these components resembles that of bacteria. It is thought that ribosomes derived evolutionarily from bacterial cells that became part of a larger cell.
  10. Cytoskeleton: worst representation ever in the diagrams. We will look more at this later. It is a network of fibers made of the proteins actin (microfilaments), tubulin (microtubules) and Keratin (intermediate filaments…actually, there are many forms of each of these proteins). Microfilaments and microtubules are constantly changing. Microfilaments are usually involved when cells are migrating, are found more at the edges of the cell and at points where cells are attached to surfaces. Microtubules all grow out of centrioles or similar structures (generically known as “microtubule organizing centers” or MTOC). In a generic cell, that usually is the centriole, near the nucleus. However, the tail of sperm and many other things that stick out of cells and allow them to move (wag like the tail of sperm…called either “flagella” or “cilia” are made of microtubules and they each require their own set of centriole-like structures). Intermediate filaments are more permanent and are used to link cells together in very strong tissues (like skin). You only find them in cells that aren’t going any where anytime soon.
Unique to plants:

Cell wall: cellulose-based structure that provides rigid “box” around cell.
Vacuole: large, fluid-filled region of the cell, surrounded by membrane. Used to maintain pressure in the cell, keeping the cell pressed out against the cell wall.
Chloroplast: site of photosynthesis. Like the mitochondria, these have their own DNA, ribosomes and tRNA. They also appear to have been bacterial in origin…long ago.
“Higher” plants (all the plants you know well…except maybe kelp, don’t have true centrioles. This is really a distinction without a difference. They have MTOCs, but lack the clear cylindrical tubes that we call centrioles.
Plasmodesmata: holes in the cell wall that allow direct diffusion of medium-sized things between cells (we will see that animal cells have smaller pores between them called "gap junctions").
Peroxosome: similar role to lysosome.

Below I’m including some real micrographs of what the components of cells look like. I can explain the technique in great detail later, if you like. But, for now, just know that we have tools that allow us to make any structure we want “fluoresce” or “glow” in a special microscope. These are not the best images. But you get the idea.

Nucleic Acids 1

Wikipedia wikimedia commons image of a Short stretch of DNA bound by a protein called “Lambda Repressor.” DNA bases are shown in “stick model” form, sugar-phosphate backbone as red or blue pipes. Protein is shown in “ribbon” form, backbone only (no sidechains).
This is one of the ways that genes are turned “off” and “on.” In this case, it’s for a gene found in a virus that infects bacteria. But, many of the same principles will apply all over.
The Double Helix
This is a really beautiful structure. Unfortunately, the beauty lies in just how much it explained when it was first proposed, and is therefore, perhaps, hard for you to see. To me, it is astonishing. I’ll run down a few features.
Basic Structure (image also from Wikimedia Commons):
And a more detailed view:
  1. There are two strands. Each is defined by a polymer of sugar-phosphate moieties (yes, that’s a word similar in meaning to “functional group”). Each subunit is linked from the number 3 carbon of one deoxyribose, to a phosphate, then to the number 5 carbon of the next deoxyribose. Instead of calling them 3 and 5, we call them 3’ (pronounced 3-prime) and 5’. The “prime” tells you that the number refers to the carbons in the sugar, as opposed to a carbon in the rings of the “base.”
  2. Thus, each strand has a chemical polarity. What I mean is that each strand has a 5’ end and a 3’ end, just as protein has an amino end and a carboxyl end. That, it turns out, is not a coincidence.
  3. The strands are aligned “anti-parallel.” The 5’ end of one strand of the double helix is aligned with the 3’ end of the other.
  4. The information is encoded by the “bases,” which protrude from the polymer backbone. This is really one of the key points: DNA is a code. The sequence of bases stands for something else. The main thing a DNA sequence stands for is the sequence of amino acids in a protein. A good first definition of “Gene” is: a stretch of DNA that encodes a protein.
  5. The information takes the form of hydrogen bonds. This is more profound than it seems: information is energy. Adenine has a much greater ability to bond to Thymine than to Cytosine; Guanine bonds much more tightly cytosine. Thus, we have A-T pairs and G-C pairs. Each base “complements” the one it pairs with in terms of hydrogen bonds it can make. We use the term “complementarity” to describe this.
  6. Now, for some interesting stuff: DNA is redundant. I only have to see one strand to know what the sequence of the other is. Each stand has all the information needed to specify its opposite strand. When there is damage to one strand, the other strand tells you how to fix it. To replicate, each strand directs the synthesis of its mate.
  7. The information is in the hydrogen bonds...and it’s a code that specifies the primary sequence of proteins (among other things). Yes, I am aware that I too am being redundant. It’s important. The DNA and the peptide sequence are “co-linear.” The 5’ end of a gene corresponds to the amino end of the peptide chain. The 3’ end of the gene corresponds to the carboxyl end of the protein. Each group of three bases in a gene is a “codon,” specifying what amino acid goes in the corresponding place of the protein...Obviously, some fascinating machine and lots of regulation must go into that. I could go on and on...but I won’t just yet.


  • ATP
  • This is ATP (adenosine triphosphate). You’ve heard of it in terms of an “energy source” for your body. That’s true, as far as it goes. However, It is also one of the four bases that are the building blocks of RNA. The difference between this and dATP (“d” for “deoxy”) is the presence of that oxygen on the 2’ carbon. (Note, when I draw it, I usually have the protons removed from the phosphates. It’s an acid and will deprotonate under most conditions in the cell. this diagram I lifted happens to have the phosphates protonated).
  • Here are three important differences between RNA and DNA:
  • There is the extra oxygen.
  • RNA is almost always single stranded, but that strand can fold back to form stretches of helix. Remember that if you fold a strand back, the arrangement is antiparallel, which is the way nucleic acids align when pairing.
  • The rules for base-paring are the same…except that a different pyrimidine, “Uracil” or “U” stands in for Thymine. It’s pairing is no different. It just lacks a methyl group on the pyrimidine ring.
  • All RNAs in the cell are made by making a copy of DNA. That is, there is DNA in the cell that corresponds to all the types of RNA we have. This will expand our definition of “Gene” a little.
  • There are three main types of RNA in the cell (that’s a lie…there are more). But, the three main types for now are:
  • mRNA: the message form of the code. The mRNA will look just like the coding strand of DNA, except it will have uracil instead of thymine (and have the 2’ oxygen). The machine that translates the code into a protein sequence does not read the DNA directly. mRNA is sort of a "buffer" copy of the information. DNA, in this analogy, is the permanent "archival" copy of the gene.
  • rRNA: The structure of the machine that reads the code and synthesizes protein. This machine is called the “ribosome” and actually includes proteins as well. It is the RNA that is the major player.
  • tRNA: transfer RNA is the “adapter” molecule. It is an RNA and therefore can “read” the code using base-pair rules. But, at one end of it, there is a specific amino acid. So, the tRNA that reads the codon UGG in messenger RNA will have a phenylalanine attached to the end of it, because UGG is a “codon” for phenylalanine (phe, or simply “F”).
  • Below is the structure of the Phenylalanine tRNA.
  • 220px-TRNA-Phe_yeast_1ehz
  • Notice that it has a detailed structure, not unlike a protein. In this case, the “secondary structure” is mediated by base-pairing. Where protein has helices and sheets, RNA has “stems” and “loops.” I’m pretty sure you can see in the cartoon to the lower right of the structure what a stem and loop is. The stems are regions of base pairing and loops have free, non-base-paired bases. That blue loop at the bottom is the “anticodon loop.” In the gray section it has the sequence 5’ CCA, so that it reads the 5’UGG codon. It may seem more natural to write the anticodon as ACC to show that it pairs with UGG. However, I will almost always write 5’ to 3’.
  • It also has tertiary structure, folding up in the “L” shape you see. That is also mediated by base pairing and other interactions.
  • You know it’s funny, you would think looking at this structure that we would have guessed that RNA like this could have protein-like functions. I mean…it has structure and functional groups (the most important ones, I"ve told you). Well, nobody guessed it (except Francis Crick). But, it turns out to be true. I’ll talk more about that later.
  • The wikipedia entry has some nice, simple pictures of translation--the making of proteins using the mRNA sequence as a guide. We’ll cover that later. But, if you want to take a look.

Protein Folding Blog

Protein Structure: Overview

Amino Acids

You should know the basic structure of one, identify the amine, the alpha carbon, the “R” side chain and the carboxyl group (acid). My goal would be for you to be able to recognize most of them. But, the main thing I want you to learn is the categories: which are charged, which are hydrophobic etc. there is a good chart in your book. Given an example, I would like you to be able to identify whether the "R" side chain is hydrophobic or what other important functional groups it has. Example: presented with serine:
you should be able to spot that the side-chain has an OH (top) on it. You could guess that it is a decent H-bond donor. You might also ask whether that OH is ever chemically attacked by a phosphate (it is, quite often).

Primary structure

Primary structure is nothing other than the sequence of amino acids that make up the proteins. While I don’t want you to sit and memorize the structures (well, I kind of do, but it’s a lot of memorization), I do want you to get to know the categories as they are identified in the book or at wikipedia. We haven’t gone into that yet. So far we have ignored the “R” groups.
Primary structure just gives you one long chain, like the chain of magnetic beads.
You should understand the chemistry of how amino acids connect to form peptides (dehydration synthesis). At typical peptide will include hundreds of amino acids. Notice that there is an
amino terminus and a carboxyl terminus. There are no actual amino acids left after peptide bond formation. They are then called “residues.”

Secondary Structure

Secondary structure is the first step of how the chain of amino acids folds. This does not directly involve the R groups, though, they will have an impact. The secondary structure will be due to hydrogen bonds between the carbonyl oxygen and the amine hydrogen of another residue. Those are part of the backbone.
For our purposes, there are two main secondary structures:
ɑ helices and β sheets (often called “beta pleated sheets,” by non biochemists).
Alpha helices will be like the small helices we built with the magnet spheres. There will not be enough space in the center of the helix for other molecules, even water, to fit. They are “right handed” screws. Looking down the spiral from either direction, the spiral runs clockwise away from you.
When we used the yellow models, we saw three main features:
  • The helix is held together by backbone hydrogen bonds between a carbonyl carbon and the amino group of the fourth amino acid along the chain.
  • This structure is fairly rigid.
  • This repeating structure places all the “R” side chains on the outside (they couldn’t fit in the center anyway). A subtle result of this is that residues 1, 4, 8 etc will be on the same side of the helix.
Here is a close up of a helix in the estrogen receptor
Notice the dotted lines indicating hydrogen bonds between a carbonyl in the backbone (little red sphere for oxygen) and the hydrogen of the amine on the loop in front of it. I have labeled two amino acids. There’s the ringed histadine (you probably are almost able to spot it by now) labeled H516 (that just means it’s the 516th amino acid residue in the primary structure. The one on the same side of the helix exactly one loop further to the right is Lysine 520 (K520). It’s four residues farther along.

Why do some amino acids form helices and some not?

The other common form of secondary structure is called a “beta sheet” or “beta pleated sheet.” (See below) Why do some chains form helices and some form sheets?

Dihedral angles:

Phi Psi Angles 1These angles, also known as the “phi/psi” angles denote the rotation around the N-Carbonalpha bond (phi, ϕ) or the rotation around the Carbon alpha-Carbon carbonyl bond (psi, ѱ)
The key thing to know is that, while the atoms are free to spin around the single bonds, there is a preferred dihedral angle. That is generally dictated by the nature of the R side chain. You can force any amino acid (except proline) into the correct angles for an alpha helix. But, some are better at it than others. Alpha helices form because they are strings of amino acids that prefer the correct phi/psi angles. If you have a run of these alpha-helix-preferring residues, they form quickly into the correct structure.
Beta sheets are made up of residues that prefer a slightly different dihedral angle. Again, any amino acid except proline can fit into a beta sheet. But, some residues are better at it.
Beta sheets will be like those flat sheets we made, or, at least the two strands we made, with the magnet spheres. As with the spheres, the sheet can be made either of antiparallel strands or of parallel ones. Also like the spheres, the details of the structure will be different in parallel and antiparallel sheets. However, the wonderful beads breakdown as a nearly perfect model at this point.


Folding of proteins and structure:

Recap: proteins are made as one long strand of hundreds of amino acid residues (the largest know has over 33,000 residues). Given that the average mass of an amino acid is 110 Daltons, a “typical” protein might have a mass of 50,000-60,000 daltons and a really big one in the several million Daltons, We actually use “KiloDalton,” 1000 Daltons, as the unit of choice. So, 50,000 Dalton would be 50KD.
They are in a line and the sequence of residues is known as the primary structure. There is an amino-terminus and a carboxyl terminus. But, there are no actual amino acids left, since water was removed when the peptide bond was formed between each residue.
Secondary structure, for A.P. bio, is simplified to be alpha helices and beta sheets. There are more subtle things I want you to know. First and foremost, I want you to know that there are more subtle things. You might encounter a 3/10 helix or a pi helix (we may build them). You know that beta sheets can fold into a barrel, like the one we folded.
My wife recently solved one that is a “beta propeller.” It’s a cool variant on a beta sheet.
Secondary structure is mediated by the backbone carbonyls interacting with backbone amines.
The last thing about secondary structure I mentioned was that an alpha helix is easy to make with one side hydrophobic and the other hydrophilic by incorporating residues with hydrophobic side-chains in every fourth position. This is called an amphipathic helix. Beta sheet have side-chains that alternate Up/down along each strand.
Structures with lots of alpha helices tend to be soluble in water. Beta sheets, not so much.
Remember that, while the “R” groups or side-chains of amino acids are not directly involved in secondary structure, they influence the dihedral angles and thereby indirectly determine what will form.

Tertiary structure:

This is the first aspect of structure that is mediated directly by the “R groups” or side-chains. The side chains influence the preferred dihedral angles and therefore influence secondary structure. But tertiary structure results from how helices and sheets come together in a 3-D shape.
Tertiary structure may be mediated by hydrophobic interactions, leaving the hydrophilic faces on the surface if the protein is found in water. But, there may also be “salt bridges” formed by interactions between negatively charged (Acid) side chains on one section with a positive (Basic) side-chain on another.
There also are covalent interactions, where to Sulfhydryl-containing side chains form a disulfide link. Two cysteine residues that may be very far apart in the primary structure may fold so that the structures in which they reside come close together. They can then form a covalent link:
This is an oxidation, as two electrons are removed. It looks like you would get hydrogen gas out. But, usually, the electrons go somewhere else.

Quaternary Structure:

This is when two or more folded polypeptide chains interact to form a larger structure. These are mediated by the same interaction as found in tertiary structure.

Lipids and such.

  • Your Bio book has intro to lipids starting on page 74. It looks at most of what I cover here.
  • We didn't get to cis and trans double bonds. But, this includes a description.
  • Outline

  • You must know the classes of lipids, how to spot saturated and unsaturated fatty acids, trans and cis double bonds and know how those things affect the interactions among fatty acids. You must be able to read a “shorthand” structure (applies to proteins and sugars too). You must be able to identify a mono, di or triglyceride (really "mono, di or triacylglyceride). Among diacylglycerides, identify a phospholipid and describe how they form a lipid bilayer. You should know that the fatty acids become attached to glycerol via a dehydration synthesis step, similar to what happens with both peptide bonds and glycosidic link. You must know that the membrane of the cell, the plasma membrane, is made of phospholipids, primarily (it also includes lots of proteins, cholesterol and other stuff). Phospholipids are probably the most important class for our purposes. We will talk about them again when we do membranes.
  • Note, most images below are taken from Wikicommons. The others were constructed with the program “chemdoodle.”
  • Lipids

  • We break lipids into two classes that don’t look a lot alike, but are both hydrophobic. The first are called sterols, which are based on this structure.
  • There are four carbon rings, three of which have six carbons and one with five. There is hydroxyl at the end. That’s what makes it an alcohol (ol ending).
  • simplesterol
  • The most well known of the sterols and most abundant in you is cholesterol, which looks like this:
  • Cholesterol
  • While you have heard that cholesterol is bad in your diet, it actually is an important molecule you need to live. You make it in your body, as do all animals. In addition to cholesterol, all the steroid hormones are based on the sterol molecule (for example, testosterone and estradiol, which we saw in the essay on structure).
  • That’s pretty much all you need to know about sterols for now. We will revisit them when we look at hormones.
  • CisFA
  • Fatty Acid-based lipids

  • As noted above, those structures are Fatty acids. These are the components of the other class of lipid. They comprise a chain of hydrocarbon with a carboxyl (acid) group at the end. We start counting carbons at the carboxyl group. The one above has 18, as noted.
  • Saturated or Unsaturated

  • These terms originally referred to whether a fat could accept more hydrogens into its structure. However, what that means structurally is whether it has any double bonds. Recall that carbon must make four bonds total. At the site of the double bond (carbons 9 and 10) in the middle of those structures above, the two carbons have only one H each. If we break the double bond, we would have to add one more hydrogen atom to each. So, that bond is “unsaturated.” This would be known as a monounsaturated fatty acid. In the popular media, that’s usually shortened, incorrectly, to “monosaturated.”
  • In contrast, a saturated fatty acid has no double bonds.
  • Cis and Trans

  • Cis and Trans ONLY apply to positions where there are double bonds…that is, unsaturated bonds.
  • Note that the bottom structure has a big kink in it whereas the other one is fairly straight, like a saturated chain.
  • Pasted Graphic 3
  • That’s because the carbons cannot rotate around the double bond and you therefore have two different ways to arrange the bond: the long carbon chains on the same side (both down in this case) of the double bond. That’s known as “cis” and results in the kink.
  • Or, the long chain on one side goes “up” and the one on the other goes “down.” That is known as “trans” (opposite directions) and results in a fairly straight molecule.
  • Trans fatty acids generally are not found in biology. The Cis fatty acids are important because of the kink. The kink keeps the fatty acids from sticking together as well and lowers the melting point of the fat. Plant oils (not from the tropics) tend to have CIS unsaturated bonds and are liquids at room temp. Animal fats and tropical plant fats tend to have saturated fatty acids and be solid.
  • Trans fats occur almost any time you chemically treat (or even heat) fatty acids with double bonds.
  • Mono-, Di- and Triglycerides

  • These are all fatty acids attached to glycerol, a three-carbon chain with an OH on each carbon.
  • The Mono, di and tri refer not to the number of glycerols, but the number of fatty acids stuck to the glycerol. I know…dumb naming scheme.
  • Once the bond is formed, since an OH is taken off the acid and an H of the hydroxyl, it is no longer a fatty acid (it’s a fatty ester).
  • The synthesis is another example of dehydration synthesis.
  • Pasted Graphic 12
  • This is a triglyceride, also known as a “Fat.” It’s primarily for storing fatty acids for use in membranes or for energy. In this case, there are three very different fatty acids on the glycerol. You can also see the alternate numbering of the “alpha” and “omega” carbon. But, again, don’t worry about that.
  • One misleading thing in this structure is that the double bonds are Cis, but the person drawing it has left out the kinks.
  • Phospholipids

  • These are the main components of the cell membrane, and any membrane within the cell. They allow us to build cells with an outside and an inside, as well as internal compartments, transport vesicles (that weird “bag” the Kinesin molecule was dragging in the movie).
  • They comprise glycerol with two fatty-ester chains. On the end position of the glycerol, there is a phosphate, which is then in turn connected to some other hydrophilic group (such as the amino acid, serine or the ionic structure, choline). The thing below is phosphatidylcholine:
  • Phopshoplipid
  • You see the two fatty acid (ester) chains going to the right and angled to the right. You should see the phosphate.
  • The key point is this: the part on the left is VERY attracted to water and the fatty acids avoid water at all costs. If you get a bunch of things like this together, they will arrange in the only way that allows each part to be where it wants. They will line up in two layers, fatty acid tails pointing toward each other and lined up alongside, with the hydrophilic part out.
  • This depiction from Wikipedia LipidBilayer
  • is a good one because it shows how thick the membrane is. It is bad because it doesn’t tell you what comes after the phosphate. Remember, though, I told you that varies all over the place. It just has to be hydrophilic. The completely hydrophobic (dehydrated) area is about 3.5nm thick. A nm (nanometer) is 1/1,000,000 of a millimeter. The membrane is about 35 carbon atoms thick.

Energy Blog

(If you want to skip my "capacity to cause pain" intro in which I imagine throwing things at you, you can jump down to "Let's make a law" below).
What is Energy?
This is trickier than it may seem, but it's very important that we have some understanding. One common definition is the capacity to do work. This begs the question: "what is 'work'?" Well, if you look that up, you find that work is a form of energy...that didn't help much.
I prefer to think of energy as "the capacity to cause pain." Yes, that's something of a joke, but it works better than you might think. Remember, the goal here is to come up with some way to relate things to each other. Pain is pain...we can all relate to it, no matter what causes it.
Imagine this: I'm standing before you with a spherical object I plan to throw at you; what are the things that matter to you? As the object is flying at your head, what determines how scared you are?
  1. how fast is it coming in at my head? (meters/second )
  2. how much does it weigh (or more properly, how much mass does it have, since it would hurt just as much if you were in space and the object were 'weightless'). Mass is in Kg.
Which do you care more about, the mass or the speed? This might not be so obvious, but some objects with low mass can cause a great deal of pain if they are traveling fast enough (e.g. think of a bullet). So, velocity matters more than mass. Based on this we can come up with an equation for how much pain the object will cause as KE=1/2mv2 where "KE" stands for the pain it causes. Actually, "KE" means "Kinetic energy," or the energy of motion. The reason for the 1/2 is not something I'm going to address here.

The units of pain
It's worth thinking about the units for this measure of capacity to cause pain. Mass is in Kg (kilograms) and velocity is in meters/second. So the units of this pain, KE, are Pasted Graphic 1 .
More Pain
Okay, let's suppose this time, instead of throwing the object at your head, I'm holding it over your head and I plan to drop it (I'm really turning out to be a mean S.O.B. aren't I). Now, what matters to you?
    1. What is its mass? (kilograms, Kg)
    1. How high is it above your head? (meters, or "m")
    1. What planet are we on?
Did that last one surprise you? Well, unlike the last example, it will matter whether we are in space, or on the moon, or here on Earth. If we are in outer space and there is very little gravity, I can drop something massive over your head and it will just float there. No worries. Gravity (g) is described in terms of acceleration, which is in units of Pasted Graphic 2. So, I can write an equation for this pain: PE=mgh , where "m" is mass (in Kg), g is acceleration due to gravity in Pasted Graphic 2, and "h" is height (in meters). Here's something interesting: the units of this capacity to cause pain are again Pasted Graphic 1 , the same as the units when I am throwing something at your head. Hmmm...seems like I have the beginnings of a relationship here.

What else causes pain? Well, I could slap you...but that would probably be against the law. Besides, it's the same as the first case: how fast is my hand moving (squared) times how massive my hand is.
It Burns!!!
Another thing that causes pain is when something is very hot. The connection to the other cases might not be so obvious. But, let's suppose for a moment that the hot thing I'm touching is made of particles (I'll give you evidence for that soon) and temperature is related to how fast these particles are moving. Even in a solid, they are vibrating. The higher the temperature, the faster they are moving (some of you may already know that temperature is a measure of average Kinetic Energy). I can give you evidence to support this soon too, but it probably seems intuitive.
So, why does a thing at high temperature hurt? Because you are being hit by particles...yes, they are small, but there are a lot of them and they are moving very fast. In fact, the average velocity of molecules in air at room temperature is about 500m/s (about 1100 miles per hour). Temperature is a measure of the kinetic energy of the particles. So, again, we have the pain being related to 1/2mv2 and we have units of Pasted Graphic 1 yet again.
Work, work, work:
So, we really have established the units of Energy, or, the capacity to cause pain. Okay most people talk about energy as capacity to do work. So, how should we define work? One type of work is when you lift or move something. Suppose you run out of gas and have to push your car. If you push on it, you are applying some force, so work must involve force. But, if you don't succeed in moving it, you haven't actually accomplished any work (in terms of moving the car, anyway). You have to move it some distance in order to do work. The farther you move it, the more work you have done. So, work is defined as force times distance–the amount of force you are applying, times the distance over which you apply it. You may remember from physics, F=ma (mass times acceleration), which means units of force are Pasted Graphic 3  (we give this a special name, 1Pasted Graphic 4 =1 Newton, or 1N). If I multiply that times the distance I move the object, I get Pasted Graphic 1 , the same units we had above. So, these really are the units of energy. If that's the case, maybe we should give those units their own name, rather than having to write Pasted Graphic 1 all the time. So, Pasted Graphic 5 . Joule is abbreviated "J" and comes from the name of another famous dead guy, James Joule (you will become very familiar throughout the year with the “Famous Dead Guy” rule for naming units).
Let's make a law:
Or, let's make two. For now, we are going to do so without any theoretical underpinnings. We are just going to base it on observations.
  1. First, let's say that energy does not get created or destroyed in normal processes, just converted from one form to another. This law is called the first law of thermodynamics.
  2. Energy will tend to distribute evenly in the space available to it. This is one way to state the second law of thermodynamics. In it’s most general form, it says that a quantity called “the entropy of the universe” will always increase. Some books refer to entropy as a measure of disorder. But, that’s not really a good way to look at it. There is a very useful statistical definition of it I will save for later. For now, increased entropy means that the energy and mass have become more evenly and randomly distributed.

A bowling ball at the top of a cliff has potential energy (PE=mgh). If I let it fall off the cliff, the potential energy decreases as the height drops. So, where does it go? Well, the ball moves faster, which means that its kinetic energy (KE=1/2mv2) is increasing. It turns out that the total increase in KE exactly matches the loss in PE. The reason I stressed "total" is that some of it goes to heat up particles in the air and the ball through friction. If the temperature of the air goes up, that's an increase in KE also. This fits with our law that energy is not created or destroyed, just converted between types of energy. Can you think of other examples?
Suppose that you have a tank of water and you stir it up and make some waves in it. You have just put energy into it, right? All the particles will be moving, so they will have Kinetic Energy (KE). Some will be in the tops (crests) of the waves. Particles in crest of a wave will be above the level of the water, so they will have gravitational PE, and will tend to fall back to the flat level. Over time, the water will calm back down and be flat on the surface.

What happened to the energy? Is it gone? Actually, no, all the energy will be in the form of KE uniformly distributed in the water, measured by its temperature. So, if our first law is right, the energy increase resulting in the gain in temperature (kinetic energy of the molecules) will be the same as the energy that you put into making the waves in the first place (James Joule, the famous dead guy for whom the unit of energy is named actually determined that the increase in temperature corresponded to the input kinetic energy). So, the energy is still there...it's just harder to recognize because it has become evenly distributed in the tank. That it tends to do that is our second law. It’s also worth noting that once the energy is evenly distributed, it is no longer very useful. You cannot do work with it.

The second law basically suggests that there is a "landscape" of energy analogous to the surface of the water, and it will tend to get flat and even over time. If there is one place that has more energy (kinetic or potential) than a spot next to it, the energy will tend to flatten out so that there are no peaks and valleys unless there is some barrier that keeps that from happening.

Think of some simple examples of this. Suppose you have a hot brick sitting in the middle of a room. Over time, the brick will cool down and the room will warm up. Eventually they will be the same temperature, which means all the particles will have the same average kinetic energy. There is no loss of energy here. At the start of the experiment, the particles in the brick had higher KE than those in the air in the room. They end up with uniform KE. Again, you go from energy concentrated in one location to energy evenly distributed.

Here's another one: suppose there is a ball sitting on the top platform of a ladder. It has potential energy. Even a modest nudge will push it off, and the ball will drop. When it settles on the ground, the potential energy is gone, converted to kinetic energy, eventually passing to kinetic energy of the particles the ball interacts with. The air particles and the molecules in the floor will each increase in kinetic energy (temperature). That is, the ball falling will convert the potential energy that resided entirely with the ball into kinetic energy dispersed among the particles in the air and floor (some of which is sound).
So, as was the case for the waves, high potential energy is an unstable state. Things at high PE will eventually fall to a state of lower PE because, when they do, they distribute the energy more evenly.
In the example of the ball, it only takes a small nudge to knock it off the ladder. Thus, chances are it will fall sometime. Now, if the ball were in a bucket glued to the top of the ladder, it would take more than a small nudge and it would not be as likely to fall. So, just because something could go to a lower potential energy, doesn't mean it will. The sides of the bucket represent a barrier to the energy distributing evenly.
Things in a high-energy state will tend to move to a lower energy state, so that energy will become more evenly distributed.
This is the big principle we have been working toward . This ultimately is why things happen.
Analogous to gravitational potential energy, there is a thing known as chemical potential energy. And the same things apply to it. Why does gasoline burn? Because when it does, the chemicals end up at a lower state of PE (like the ball falling) and pass the difference in energy onto the surroundings as heat (Some of it can be used to do work, like moving your car).
That’s another big theme: even though there is no net loss of energy, the transfer of energy can be used to do work. Once it is all evenly distributed, there’s nothing you can do with it.

The Big Rule

Energy will tend to distribute evenly (entropy will increase). Because particles carry kinetic energy (unless they are at absolute zero), the distribution of particles will tend to become random over time because that distributes their energy. Why doesn’t everything fly apart into random distributions? Well, the universe as a whole seems to be heading that way. But, locally, things can stay fairly ordered-looking. Biological systems in particular seem very ordered.
It turns out there is another way to distribute energy more randomly: form bonds. You see, forming bonds always releases enthalpy, which can be loosely thought of as heat, to the surroundings. Conversely breaking bonds always requires input enthalpy.
This seems like forming bonds should be favored by our laws. If I release heat to the surroundings, I impart that energy to the surrounding particles, which can then distribute that energy more randomly.
But…there is a tension here.
Let’s consider the melting of ice or freezing of water. Most of you did a lab in the beginning of last year in which you saw that as water froze, heat was released to the surroundings. That’s consistent with what I just said: forming bonds releases enthalpy. That’s good because that released heat gets to distribute more randomly. But, forming bonds also restricts the motion of the molecules (in this case, water molecules become ice). That’s bad, because whatever kinetic energy the water molecules have gets pinned down in the crystal and can no longer distribute as widely.
On the other hand, when ice melts, the particles get to distribute more widely, carrying their energy and distributing it more randomly. That’s good. However, breaking the bonds of the ice crystal requires input enthalpy. That takes energy from the surroundings, cooling it down, and concentrates that energy as higher potential energy in the water molecules. That’s bad.
So, which one wins? Is it more energetically favorable for the bonds among the water molecules to form, releasing enthalpy to the surroundings, but constricting the molecules themselves? Or, does the freedom of the water molecules to move around win out? Does ice melt spontaneously or does water freeze spontaneously? The answer is, it depends on the temperature. And if you understand why, you understand a lot about energy.
At temperatures above 0
oC (273K), pinning the molecules down is more costly. The higher the temperature, the more kinetic energy the molecules have, the more they are able to break the bonds holding the ice together, or, more correctly, the greater the benefit to letting them move freely. At temperatures below 0oC, however, the cost of taking enthalpy from the surroundings and using it to break the bonds is not offset by the benefit of releasing the molecules.
Notice while at really low or really high temperatures, you are likely to have all ice or all water. But, right at 0
oC, you can have both ice and water. And, you can nudge it one way or the other by making relatively small changes to conditions. That’s because you are right at the point where the two players in the tug of war are equal to each other. This will be an important consideration in biology too.
We will come back again and again to breaking and reforming interactions. It is absolutely imperative for life that virtually all the reactions in our body be reversible, favoring one direction under some conditions and the other direction when those conditions change. We eke out a living at the margins of free-energy differences, always paying for it by heating up the surroundings (releasing enthalpy) satisfying the rule that we must increase the entropy of the universe.

A biological Example:

By now you have heard “DNA contains the information that specifies living things.” Or perhaps you’ve heard it called a “blueprint.” You almost certainly have seen representations of it as a “double helix.” You may even have heard that “A” binds with “T” and “G” binds with “C.” (The four “bases,” are Adenine, Thymine, Guanine and Cytosine are abbreviated by their initial letters). But, how does DNA encode information? Why do “A” and “T” pair and not “A” and “C”?
Well, for one thing, adenine sometimes will bind with cytosine…just poorly and less stably. This is one way that mistakes, or mutations, happen when DNA is copied. The reason A binds with T most of the time and better than it would bind with C is simply because the change in energy is more favorable. The enthalpy released to the surroundings is greater when A binds with T than when A binds with C. It turns out that G binding with C releases even more energy.
The energy involved is very much along the same lines as that involved when ice freezes. In both cases, the bonds are hydrogen bonds, either among water molecules or between the bases of DNA.
If the analogy is to hold up, what do you think will happen to a pair of bases, A-T or G-C, if we raise the temperature? If the two strands are held together because of the same principles that hold water together as a liquid, or ice as a solid, what should happen to a double helix of DNA if I raise the temperature?
If you answered: “the bonds should break and the two strands of the helix should come apart,” you are correct. We even call this “melting,” the DNA.
This is just a first brush against a set of principles we will return to often in the coming weeks. The answer to questions like: “why do proteins fold up into their active shapes?”; “how does the muscle contract?” and many more will come down to the same simple principles, though applied in a rather complex pattern.