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How To Build A Cell

Since I was in the midst of writing a series about the non-fine tuning of the universe I decided to read a somewhat academic book from some advocates of fine tuning. Instead of the obvious apologetics of William Lane Craig and Dinesh D’Souza, I picked up a copy of Fitness Of The Cosmos For Life: Biochemistry And Fine-Tuning by John Barrow, Simon Conway Morris, Stephen Freeland and Charles Harper. The forward was written by George M. Whitesides who is a Chemistry professor at Harvard and that is the reason I am writing this.In the forward George Whitesides writes

The complexity of the simplest cell eludes our understanding – how could it be that any cell, even one simpler than the simplest that we know, emerged from the tangle of accidental reactions occurring in the molecular sludge that covered the prebiotic earth? We (or, at least, I) do not understand. It is not impossible, but it seems very, very improbable.

I must congratulate him for admitting that the self assembly of a cell is not impossible but I do not fully understand how he can claim it is improbable considering one area of his research is the self assembly of molecular structures and another is the origin of life. Not only are two areas of his research self assembly and the origin of life but it has been an area of immense research (self assembly of cells) since the 1960s and it is inconceivable that it was not known to George Whitesides.

In the rest of this article I will attempt to explain, keeping the chemistry to a minimum, how and why a cell can self assemble and what are the requirements that will allow that to happen. Before I begin I will say that already in this area of research not only have vesicles been shown to self assemble but they have also been shown to capture larger molecules inside. They have also been shown to grow when given access to the same lipid as in the bilayer of the vesicle. Lastly, they have been shown to split (reproduce) when subjected to ordinary shear forces as found in tidal pools. Additionally as if it really needed to be said the daughter vesicles after the split have grown after being exposed to the lipids that compose their bilayer. After writing this out, I changed my mind, it is not inconceivable that George Whitesides was unaware of this, it is however quite understandable that he ignored it so he can keep his extremely high Hirsch index (he holds the highest number among living chemists). Then again, the funding for this book came through the Tempelton foundation so it isn’t too surprising that valid science is ignored if it contradicts their goals.

The great theoretical physicist Freeman Dyson in his famous garbage bag model said

The early cells were just little bags of some kind of cell membrane, which might have been oily or it might have been a metal oxide. And inside you had a more or less random collection of organic molecules, with the characteristic that small molecules could diffuse in through the membrane, but big molecules could not diffuse out. By converting small molecules into big molecules, you could concentrate the organic contents on the inside, so the cells would become more concentrated and the chemistry would gradually become more efficient. So these things could evolve without any kind of replication. It’s a simple statistical inheritance. When a cell became so big that it got cut in half, or shaken in half, by some rainstorm or environmental disturbance, it would then produce two cells which would be its daughters, which would inherit, more or less, but only statistically, the chemical machinery inside.

One thing I would like to address before I get into the actual chemistry side of this is why I (and apparently lots of scientific researchers) feel that a cell or rather a proto-cell or vesicle is a necessary component before life can begin. Let’s look at it in  this way, the emergence of life was a simple chemistry experiment and life could not emerge until the correct chemicals were combined under the correct conditions. Unquestionably there were many different chemicals available on the prebiotic Earth and just as in a university Chemistry lab where chemical experiments are done, a means of encapsulation is necessary to separate the chemicals that are needed in the reaction from those that are not necessary. This conveniently is done by naturally forming lipid bilayers called vesicles. These vesicles which are formed by a  two molecules thick layer of lipids (hence the term bilayer :)), are natures equivalent of the chemistry labs test tubes and beakers. Without test tubes and beakers chemistry experiments would be near impossible and without a proto-cell first (a natural test tube), the grand chemistry experiment that led to the emergence of life would in fact be very improbable. That point I will agree on with George Whiteside but everything I have written above was known to him prior to his writing what he did and everything above unquestionably reduces the near improbability to an inevitability.

Now to the fun part. What is required for vesicle formation? First and foremost a source of amphiphilic hydrocarbon chains are required. Whether you consider the source to be a carbonaceous chondrite such as the Murchison meteorite or naturally formed on the prebiotic Earth the correct molecules were available. One of the reasons why research into life’s origin based on a cell first approach was not done till comparatively recently was because it was thought that the length of the hydrocarbon chain necessary to create enough impermeability was longer than what was available on the prebiotic Earth and that impermiability would prevent necessary chemicals from entering the proto-cell, also the length necessary for the stability of the proto-cell (modern cells use lengths between 16 and 18 carbons) again was not available on the prebiotic Earth. That definitely would have put a major obstacle in the path of a cell first approach but there are two small problems with that critique. Firstly impermeability is not an either or proposition as there is a vast range, just look at how oxygen diffuses from red blood cells (in less than a second) while glycerol will diffuse across cell membranes within a few minutes. As far as the stability problem, looking at the hydrocarbon chains in carbonaceous chondrites as an example (specifically the Murchison meteorite) the lengths were between 9 and 12 carbons long, could stable vesicles be formed by those short chains? Those of you who read my other articles could probably figure I am going to answer this affirmatively. In 1978 a then young graduate student named Will Hargreaves found that phospholipids (phospate group at one end of the chain) can self assemble into stable vesicles with a length as short as 10 carbons. Another graduate student in the same lab named Stefan Paula showed that permeability in the membrane could be increased by simply shortening the chain length. So much for the seemingly impenetrable hurdle to a cell first origin to life and research began in earnest.

Now one can ask what is necessary for the amphiphilic hydrocarbon chains to self assemble? Short answer is four “forces.” They are covalent and hydrogen bonds, Van der Walls forces (electrostatic) and hydrophopic effects. I am not going to address covalent bonding as a separate topic since I can’t do that topic any justice with a short paragraph but I will discuss the remaining three “forces.”
Hydrogen bonding helps to stabilize the structure of the self assembled vesicle. Saying that is all well and good but it would benefit us if I were to explain hydrogen bonding to those readers that don’t have a chemistry background. Once again without delving into too much chemistry (just formulas) I’ll give a short description of a hydrogen bond. The rotten egg smell we all hate (except those really odd ones among us) comes from a molecule called hydrogen sulfide H2S. Some of you readers might recognize the similarity to H2O which is something all of us are familiar with. The reason I bring these two molecules up is because water is a liquid while hydrogen sulfide is a gas. You might ask why that is and the answer is hydrogen bonds. They are what holds water together as a liquid and as an aside, they become pretty much continuous below freezing and that is why water freezes solid. Hydrogen sulfide remains a gas simply because it doesn’t form hydrogen bonds. Linus Pauling was the first to recognize the importance of hydrogen bonding  in the process of self assembly and of course he has an excellent description of hydrogen bonds in his 1939 classic The Nature of the Chemical Bond and the Structure of Molecules and Crystals: An Introduction to Modern Structural Chemistry. Not only did Pauling recognize the importance of hydrogen bonding, he understood that it was what stabilized the structure of DNA and prior to Watson and Crick’s discovery in 1953 Pauling proposed that DNA was a triple helix.

It is rather difficult to see what Van der Walls forces have to do with biology since it is chemical bonds that hold the hydrocarbon chains together. However the only interaction between the chains are Van der Wall’s forces (sort of like static electricity in a sense). It is Van der Walls forces that determine whether a hydrocarbon chain is a solid, liquid or gas at a given temperature.  Hydrocarbon chains up to three carbons long are gas at normal temperature and pressure. Butane which has four carbons is  balanced on a fine edge between a gas and a liquid (that is why it is used in cigarette lighters). Chains between five and ten carbons are all liquid while those of 11 and above are solid. The easiest way to see why this is is to look at the carbons as a zipper of sorts. The less teeth on the zipper (carbons are the teeth) the less “holding” force it has. The more teeth, the more force it generates. Guess the zipper makes it clearer than the static electricity similarity.

Lastly we come to the hydrophobic effects required for self assembly. The hydrophobic effects drive the separation of the chemical system from the environment. This is the reason I mentioned encapsulation earlier. Imagine without encapsulation (a test tube) what it would be like to perform a chemical experiment in the open seas. Getting back to hydrophobic effects, life itself can’t exist as a solution of molecules because molecules in solution (no matter how complex) diffuse in a random fashion. Without organization they could neither metabolize, grow or reproduce. From this it follows that all life is cellular and those cells are bound by a bilayer that self assembled from ampiphilic molecules. It is the hydrostatic effect that stabilizes the membrane.

I feel I have answered the original question asked by George Whitesides but this article is sure to have raised many other question such as how the first proto-cells nourished themselves, how the first proto-cells were able to capture and hold large molecules while allowing necessary chemicals to pass through the bilayer. The first question will have to wait for another article at a later date but the second question is one I will attempt to give a short answer for. First let me say this is pure conjecture on my part and not to be taken as a scientific theory in any way at all. Before my conjecture I’ll give you some actual science. One hypothesis is that the first nucleic acid on Earth was Threose Nucleic Acid (TNA). Threose is formed as an end product of the formose reaction which is where the simple aldehyde formaldehyde (methanal) reacts with itself and those products react with themselves ultimately ending the series with the tetrose sugars which threose is a member of. On the prebiotic Earth there were bodies of water (oceans, ponds, puddles). When a vesicle formed in a water source and was subsequently splashed onto another surface (such as a hot rock) and dried, the vesicle would straighten itself. When it got rehydrated (from rain for example) it would reform into a vesicle capturing the molecules that were between it’s layers. Ok, actual science is over now on to my conjecture. Sometimes that captured molecule just might have been TNA. It might have been another necessary molecule. Truth is we don’t know what actually happened but the scenario I put forth is certainly a plausible one and given the 750 million years or so that life had to emerge on Earth before it did gain a foothold, it really isn’t improbable and I would call it inevitable. It is just surprising that I, a man who does no research and is not on the Hirsch index (but does have an education in chemistry and an award from the American Chemical Society as George Whitesides does.) has to answer a question that he finds makes life’s self assembly without a god to be highly improbable.


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One Response

  1. I like what I see, your ideas are interesting. Please keep posting!

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