On Micelles, Vesicles and Artificial Cells

-The magic of directed self assembly

This post is a collection of thoughts on the principles of entropy, energy and equilibrium expressed in the context of self assembly of surfactant molecules [1]. Let us begin by asking what a surfactant is. For the purposes at hand, a surfactant is a molecule with a small head that likes water and a long tail that hates water as shown in the cartoon alongside. What “loves” means in the following is that the entity can lower its energy by being in contact with water and what “hates” means is that it costs the system a lot of energy when it is in contact with water [2]. Now, we put a bunch of these surfactant molecules in water and allow them to come to “equilibrium”. What do they do?

To understand this question, we have to first clarify what a system will like to do. The equilibrium state of the system will be one where it can do the maximum number of things it likes. The first thing the system likes to do is lower its energy as much as it can. On the other hand, the system likes to have as much disorder as possible, technically speaking, “maximize its entropy”. If I call the energy of the system E and the entropy of the system S, then the system likes to have a minimum value for the quantity F = E – TS, and this is called the free energy of the system. Don’t let this little jargon scare you. What follows is simple enough even if you don’t remember this. Also, before we can guess what the system will like to do, we need to know one more thing about the surfactant molecules. If two surfactant molecules come close to each other, what would they do? The tails of these molecules are such that they are happiest when they are as close to each other as they can get, for they lower their energy by reducing their interaction with water and increase their entropy as well [3]. The heads of these molecules are such that they want to stay as far away from each other, because these heads are usually charged and like charges repel right? So they lower their energy by staying away from each other.

With that, we have all the ingredients we need to answer the question we asked. It is now all about a competition between love and hate. Suppose the heads love water way more than the tails hate it. Then the equilibrium state of the system will be a solution of the surfactant molecules in water, with all the molecules well separated from each other and doing their own thing [4]. Next, suppose the circumstances are that the hate of the tail wins. Also, suppose that the heads are wide objects so that the overall shape of the surfactant molecule is a cone (see figure). Then, the molecules are happiest when they form micelles. Micelles are objects that are spheres, with the polar heads outside near the water and the tails inside, talking only to each other and protected from the water by the polar heads. Note that, in order to form micelles, you need a given amount of surfactant in the water (If you have fewer surfactant molecules, entropy wins and they stay in the form of the solution). The everyday situation under which micelles are formed is when you wash your clothes with soap. The dirt on the clothes form nucleating centers for the micelles and the micelle itself being water soluble, dissolves in the water when you rinse your clothes.

The more interesting case is when the heads are not fat, i.e., the surfactant molecule is a cylinder rather than a cone (see figure) and still the hate of the tails wins. In this case, the system forms what are called “lipid bilayers”. This is just two layers of surfactant molecules assembled such that the tails of each layer face each other (effectively, it is like having a layer of oil trapped between two layers of polar heads). Now, in this structure, the tails in the middle are clearly happy for all their neighbors are fellow hydrocarbons. But, just as clearly, the tails at the edge of the structure are unhappy because they have to talk to the surrounding water. One way to eliminate this is for this bilayer to fold on itself to form a spherical shell (see figure, which displays a cross section of such a structure). This way, there is no surface of tails talking to the water. But the trade off comes at the cost of forcing the heads in the inner layer to be more close to each other than they like. But, if the hate of the tails for water is large enough, this happens and the resulting stable structure is now a vesicle!

The interesting things to note here are twofold. One, in spite of the language I am using, in the actual experiment, all I did was take a spoonful of surfactant molecules and put it in water. All the structures mentioned above self assembled! I did not have to do a thing. The second thing to note is that, the above vesicle is essentially a minimal cell membrane, the first step towards the process that converts an auto catalytic chemical reaction into what we call now as life!

So, if we can make this membrane functional, namely, make sure that the chemical machinery required for life is trapped inside the vesicle, make appropriate “holes” so the membrane is suitably permeable (i.e., it lets some stuff in (raw material for making food) and some other stuff out (waste products) and not vice versa), we would have made an artificial cell! Some first steps in this direction have already been taken. See for example, this PNAS article reporting the use of “directed self assembly” to make a bio reactor, which is to say it is not quite a cell yet, and this article entitled “Towards an artificial cell based on gene expression in vesicles” . We are not very far from making what can only be termed as artificial life, in a physics lab, in a test tube. And the reason I started thinking along these lines was to be able to ask the question – “Intelligent design anyone??” :) [5].

Caveats and disclaimers

[1] The aim is to try and keep things simple, focusing on the primary ideas and suppressing all but the bare essentials in terms of details and subtleties.

[2] The jargon is that the head of a surfactant molecule is a polar group like sodium sulfate and hence this ionizes in water and hence is hydrophilic. The tail is a covalently bonded hydrocarbon polymer and hence hates the high dielectric constant medium of water and is hydrophobic.

[3] The entropy of a polymer would be given by the number of configurations they have. They can fluctuate better and sample their accessible phase space better in the lypophilic environment of other tails, than in water, where any fluctuation will result in an energy cost.

[4] It is clearly an oversimplification. The question is truly one of entropy versus energy. So, this will be a strong function of the concentration of the surfactant and the temperature of the water. At low enough concentrations or high enough temperature this will always be the default state with no possibility of self assembled structures.

[5] This is actually a frivolous statement. The stumbling block that people have to overcome is the complexity of a real biological membrane, which has embedded proteins and is active and what not. But from a physicist’s point of view, it is but self assembly, but takes a lot of time. I say this in spite of the fact that from what knowledge we have of the primordial soup and pre-life conditions on earth, there appear to have been singular events that precipitated the emergence of life in nature and we do not know either way, the probability of such singular events occurring from random initial conditions.

Ode to the unknown reader

As I had said in an earlier post, I have not been here, in the blog sphere very long. So I don’t know anything about anything and am too lazy to educate myself. But, as a matter of routine I had created accounts on a couple of the free web stats services out there. And then promptly forgot about them. Yesterday, I was badly stuck on something and needed to kill some time to allow my subconscious to mull over my confusion (that is my excuse for browsing instead of working while in my office :)) So, I went to these websites to look at the stats for this blog. Now, my lack of knowledge on how these stats are acquired prevents me from really understanding what they mean (for example, if somebody reads me through their feed reader, as some of you do, how would this show up in the sitemeter stats?). But to the extent that I do understand them, it appears that I have more readers than I know of!

Everybody knows that we see things not as they are, but rather as we are. So, my model blog sphere inhabitant is based on me. And when I read someone’s post all the way through and like what I read, 9 out of 10 times, I leave a comment, even when I don’t have anything intelligent to contribute to the topic being discussed in the post. The exceptions to this being if the blog writer is one of the more famous ones like my reptile object of admiration Sunil or the master of logic with a really erudite audience (going by his comment threads) Falstaff just to name a couple, or there are already a number of comments to the post in question and I don’t wish to add to the already redundant thread. So, I assumed that this was true for everybody else as well.

But that is surely not the case according to my stats. For example, I appear to have a couple of regular readers from my alma mater, the school that is the defending NCAA football AND basketball champs this year. And I don’t think I know who they are! And another surprise I found was that people stumbled on some of the posts from google searches! It is a surprise in two ways, one, just the fact that a page shows up within the first few results of any search at all and the second, the reader actually spent five minutes on the page they landed!

I guess that just as in real life, not a day goes by without learning something new and hence finding one more piece of a puzzle that is just beginning to take shape. Anyways, just wish to say thank you for reading. One needs at least an illusion of an audience to force oneself to think clearly and if they have a real one, all the better!

Linking park on Evolution

I have been on a spree of reading on Evolution and Intelligent design and so on to keep me entertained during my recent travels. I am sharing some of them with you in case you missed reading them. First up, 15 Answers to Creationist Nonsense, a Scientific American article by John Rennie, my respect for whom dropped several notches after reading this, which came off more as rant than reasoning. Next, the rebuttal by the ID crowd over at Apologetic press. Boy! They are verbose. I am yet to complete reading this one. While you are at it also check out the book Singularities, by Christian de Duve. I am yet to make up my mind about some of the things he says in the book. Also, as an aside, there is this wonderful article in PNAS this month, called “Darwin’s greatest discovery: Design without designer”, beautifully juxtaposing Darwin with Copernicus. I fell in love with that analogy that never occurred to me before. As always, all this “foraging for information” was so I can condense this whole “Evolution vs ID” in my reductionist no-frills language. But it needs some more simmering before that can happen. So, my own thoughts on all of this stuff follow later.

Do You Believe in God?

I got asked this question recently by somebody after a long time. This made me realize two things. First, the trivial one of the two realizations was that the fact that it has been a long time since I got asked this question is indicative of the other fact that I have not had discussions or conversations with anyone who is not a scientist of some form, and hence have kind of forgotten what that is like. The second more interesting realization was that asking if I believe in god is like asking me if I believe in the washing machine! And I want to take this post to explain to you why this is the case.

Now, every reader has to agree with me that the second question is ridiculous. Why is that? Because I can touch and see the washing machine? No, that is not what I mean. May be a washing machine is not that good an example, may be I should have chosen Energy or some other concept like that to illustrate what I want to say. What I mean is that the washing machine is an invention made to fulfill a need, namely to use a power source other than human muscles to clean clothes. In this sense god is an invention we made to fulfill another one of our needs, and a basic one at that, the need to understand.

Let me explain further. Human beings like all other organisms have needs, food, oxygen, water etc. But in addition, we have another need, that need is the need to understand. Now, suppose I lived at the times of early man. All I had for observing the world around me was my five senses. So, the length and time scales of natural phenomena I had access to were limited by that. And then I saw plants grow into trees and bear flowers and fruits and die. I watched the sun rise and set everyday and watched the stars at night and could not see them if I looked for them when the sun was around. I saw other humans die and become inanimate suddenly. I saw people get sick and did not know why as I was not able to correlate it with anything that had happened before they fell sick. Under these circumstances, I would definitely have invented god. I could explain everything that I observe using one simple concept, namely god is doing it. That is how god came into being.

Then, as people got more understanding of what was happening, for example, when they realized that the objects in the sky must be moving in circular paths relative to earth, they said such things as angels with wings (like the birds they observed here on earth) pushed the heavenly bodies so that they moved in circles and other such subdivisions and auxiliary stories branching out from the concept of god emerged. Then, they wanted to divide observed phenomena into two groups. The first group consisted of those things that were good for humans. The second was those that were detrimental for humans. The second class of phenomena they decided should be propelled and caused by a different unifying entity. This became Satan, or Asuras or whatever the local word was for it. And in this subdivision of phenomena, they included the emotions they themselves felt. If you were jealous, that is not good for the group dynamic and hence you were advised to pray to god to overcome this “temptation of satan” or whatever jargon was fashionable at the time.

So, what about now, in today’s world? First of all, our knowledge of all things is exponentially larger. Not only can we see on all scales (scanning tunneling microscopy and atomic force microscopy now give you subatomic resolution to see things and cosmological observations let you see way in the past, into the very early universe), we have been thinking collectively as a species for long enough that most of the observed phenomena is tied into neat theories with only a few basic assumptions and these assumptions are way simpler than postulating an all powerful entity that did everything. And there is a change in attitude as well. We still don’t know many things. For example, we don’t know how to cure Alzheimer’s or even a simple viral infection. But, we don’t decide that we should all spend time praying. We pay taxes so that the people who know about such things can find out more and hence figure out how to beat these illnesses and thereby make sure that even though we will probably die of these diseases, perhaps our grand children won’t. We have come to understand the power of knowledge and are willing to trust it in some regions of our existence.

But there is one region, where in spite of all the progress made, we cannot put our trust in our knowledge yet. And that is our mind. For all the lip service we may pay to the biochemistry of the brain and the value of Freudian theory of psychoanalysis, we still cannot accept the apparent “fact” that we are but autocatalytic chemical reactions, albeit very complicated ones, but still just a chemical reaction and everything else must follow from there. I mean, even I am a little reluctant to admit that my consciousness is just chemistry and could eventually be controlled as such. So, we still need god to complete the picture we have of the world around us.

PS: These thoughts are about god, not religion and those are two very different things.

PS2: Apologies to anyone that came looking for a new post last week and did not find one. I was traveling…may be I’ll tell you about my adventures in New Mexico subsequently

Science and society – some musings

The following thoughts occurred to me after reading this post by Sunil in which he was talking about explaining to his non scientist friends what he was doing in life. Before I launch into my spiel, a disclaimer: I am talking about how things should be or must have been rather than how they actually are or were, in a sense, a rudimentary model for human society that misses a lot of the complications that are there in the real version.

Scientists are the highest (or lowest, depending on how you draw the arrows) in the societal food chain. The way to understand this statement is as follows. Each able bodied human being has a two fold existence. One is his or her existence as an individual and in this avatar, his or her primary quest is one’s own happiness. The second is as a part of the collective structure that is the society. In this role, each person has to fulfill a function in the society. For performing this function, the person derives remuneration for sustenance and may be other things as well. In each case, the function performed benefits other human beings by making their life better. For example, the farmer provides food. The electrical lineman outside my window is ensuring that everybody in my building has uninterrupted electricity. The clerk at the bank this morning was making the process of handling money, the chosen denomination of resource in today’s world easier for her customers. The computer engineer techie friend that we all have writes codes to improve the function of the computer so all other things in the world that rely on his code’s ability to function may run more smoothly in the future.

Note that in each of the activities mentioned above, and in any case you can imagine that is outside basic science, the turn around time before your action benefits the society ranges from a day to a few months to at most a few years (this might be the case for people in the R & D departments of industries for example). But a scientist is different. His or her role in society is to take the frontier of human knowledge forward. Of course eventually this process will result in the improvement of quality of life of human beings. But the time scale over which this happens is several human life times, not just a fraction of one. So as far as a normal person is concerned, we are not contributing anything useful to him, for he usually lacks the ability to see beyond his nose.

Next, note that each person fulfilling a useful function in the society contributes a portion of his or her remuneration to a common authority (a geographically varying government of some form). The sum total of all such earnings is directed towards things that enhance the common good, for example infrastructure (roads, schools, airports etc.,), health care and safety and oversight organizations. And more importantly for the purpose at hand, it is from this “common good” money that we scientists derive remuneration to sustain ourselves and the resources to accomplish our research goals.

Once upon a time, when the world was simpler, it was not necessary for every Tom Dick and Harry to have the ability to see beyond his nose. The ruler of the land controlled the resources and had the ultimate say in how these resources were spent. And as long as the ruler was far sighted, he made allowances for philosophers and scientists to live off the state’s income and hence ensured that there were some people thinking about the things that the majority of the others were not. In the present day, things are complicated. And there are two reasons for this. One, now most of the world is a democracy. So in principle, every one of the Toms, Dicks and Harrys mentioned above has a say in how the money is spent. This would not in itself be such a problem if the only thing in question was remuneration for sustenance of the scientist. We all know that as far as pay checks go, a grad student in a science department makes less than the janitors in the same department and a full professor in an academic department at the end of his career has a salary comparable to a techie at the start of his. And we, the scientists, have no right to complain. Monetary benefits are something we will readily sacrifice for the privilege of being at the forefront of human knowledge and being afforded the ability to do what we love day in and day out.

So that brings me to the second problem complicating things in today’s world. The frontier of knowledge is advanced enough that questions can no longer be answered by using stuff other people threw away like Lord Kelvin did or Benjamin Franklin did. The outlay for experiments run from hundreds of thousands for some sophisticated bio-tech problems to billions for the particle accelerator experiments necessary to push the frontier of fundamental physics forward. And with such amounts in play, it reasonable for anybody to ask why the resources of the society have to be spent this way when there are millions of people that don’t even have enough for sustenance.

Now, I am not disputing the fact that money needs to be spent on the scientific questions. Human society cannot function by choosing one priority for a generation. It can only progress by making strides in all the dimensions of its existence (you can dispute this theory and I know I have to justify this better, but perhaps in a later post). I am saying that in today’s world scientists have to take the role of outreach more seriously. Every person needs to understand and acquire the scientific mindset and realize the wonders and power of knowledge the way we scientists do. It is the absence of such outreach initiatives on our part that gives rise to biblical interpretations of evolution or claims that quantum mechanics cannot be right. And when I say outreach, I don’t just mean the systematic activities that are being undertaken by the scientific community. I also mean everyday interaction between a scientist and a regular person, my techie friends, my grandmother, my neighbor, my cab driver. It is our responsibility towards society that we step down from our intrinsic (and in my opinion entirely justified :)) “holier than thou” stance and try to reach out.

On forwarded emails and common sense

I have an email address and so do you. And I get emails that I don’t particularly want. Everything from me having inherited some million dollars from some long lost aunt to offers that let me enlarge parts of the body that I don’t even have. But with improved spam blockers on the commercial email servers and my own departmental email server, most of these annoying emails don’t show up in my inbox and the few that do, I can delete easily enough with not needing to open it to figure out what it is. So this class of emails is not so annoying anymore.

At this stage, the only emails that I open before deleting are the emails from coworkers and friends. A portion of these emails are forwarded messages. Some of them are jokes or links to cute youtube videos and so on. Depending on how hectic life is when I receive such emails, I read the jokes or follow the links (a recent one I followed is this “Candy shop parody” by some desis) or just delete the email. Hence these emails are not in the annoying category yet.

The emails that fall strongly into the annoying category are the forwards that warn you about everything from spiders on toilet seats to burning aromatherapy candles to the possibility of suffocating in your own fart! You might say “why do they annoy you? If you are busy and you see “FWD:” in the subject line of an email just delete it!” But I find myself unable to do that, because I get these emails from people that are otherwise very smart and I respect them a lot. For example, the email that prompted me to write this rant came from this post doc friend of mine at IAS, Princeton, and he is one of the sharpest people I have met. I find myself unable to dismiss out right as nonsense things that people I respect send me. But I guess that is my fault, to assume that smart in one thing means smart in all things. I never learn.

In any case, what should a sensible person normally do before when one receives such an email? First use some common sense to weed out the absolutely absurd (like the last one in the examples earlier, we exhale way more CO2 than we fart) from the somewhat reasonable like the first two. Then you go to Hoax Slayer or Break the Chain or use the infinite resource that is Google to see how old this particular urban myth is and what is known about the claims. Then, you further apply your common sense if all this does not help you make up your mind. For example, suppose there was truth in the claim that you could die if you burn aromatherapy candles in an air conditioned room. The fragrance industry is a multi-million dollar enterprise in the US and companies get sued for anything and everything even if there is a semblance of truth and sure as hell the paranoia ridden media would have told you all about even the slightest health risk, perceived or established that you will never have to learn about it from a forwarded email from your grand aunt in India. So, you delete the email and don’t subject your friends to the effort of opening it and reading it.

Now suppose you are busy in life yourself and get such an email and don’t have the time to go through the process of making up your mind, but your first inclination is somewhat towards the claim. Then I think most people find compelled to pass on the warning, because of some kind of social responsibility they feel or something. But please! Spare me! If it is important I am sure to find out some other way. And if it is not, I don’t have to go through the exercise of deleting all but the most important mails in the morning, when I have woken up late because I was up late working and am running late for the first meeting of the day. Bottom line: email etiquette should require that you mark the subject of your forwarded emails as “junk”, “read at your leisure”, “just for fun” or in an unlikely scenario that I cannot even imagine right now “DON’T DELETE”.

Traveling – I like it

I am at the airport, whiling away time until my connecting flight. First, I started working, so I can get caught up on at least one of the million things I am behind on. But this is a long layover and I am getting tired. This is a common feature during my travels, I can never work for very long irrespective of how many things I absolutely need to get done in the immediate future. So, I thought I will stop and ask myself why that is.

I love traveling. Not just going places and seeing things but the actual act of getting to the various places. I discovered this on one of my never ending transatlantic flights a few years back. I hate these flights for different reasons, all that sitting makes my back hurt and invariably my nose starts to bleed from the dry air. But I like them for they are a break from routine. You are isolated in this aluminum tin 30000 feet up in the air, no way you can do anything about it till you come back to terra firma.

What this affords a restless person like me is the time to just be with my thoughts with the urge to do the million things that are up in the air at any given time in my life easily suppressed. I love that. The luxury of just being, that everyday living never affords you. This is because if you are at home or your office and in a “just be” state, then you are going to be feeling guilty at the same time for not doing the things you are supposed to be doing.

But as I get older, the “just be” feeling is getting corrupted even when I travel, as most of my work now just requires my laptop and some pen and paper and so I don’t have the excuses I had earlier in life (namely, need for books, reference papers, internet etc) for not working at airports or on planes. So, now my new mantra is my favorite form of traveling is driving. While driving, you cannot expect me to be using my laptop would you? So back to guilt free just being!!

I like traveling so much, that I even thought half way through grad school that I should just give up grad school (that was not going so well at that time) and become a traveling sales “person” of some kind. Simple life, and all the traveling you would ever want to do. Oh! I really should have followed through with that instinct, should I not?:)).