Hi,
I only wanted to be sure: Our homework for the last part is the exercise we discussed in the first class, and is to be handed in before or on the day of the exam (which we still don't know). Am I right?
Thanks
Angel

Class: December 5th 2007

We have reviewed a particular example of population dynamics by means of a model for Hantavirus spreading in a mice population. In this example fluctuations are taken into account through seasonal changes and we saw some paradoxical effects in that regard. If you want to find out more about this problem of population dynamics take a look to the following research papers covering different topics:

• Seasonal alternation effects.
  
• Internal fluctuations effects.
  

Class: December 10th 2007

Today we finished the Markov chains and posed your homework for this block. The homework is about a molecular motor where the potential landscapes of a (simply described) Kinesin moving have been discretized. We commented on the different states and transition rates to include non-equilibrium effects. In regards of this homework, I ask you to:

a) Find values of T1 and T2 (and lambda) such that a net current of "particles" appears.

b) Estimate the value of the fluxes. How can you define the current of particles in terms of fluxes?.

c) Is it possible to reverse the current in terms of the parameters T1, T2, and lambda?

Due date will be the day of the exam (whenever that date will be during January and independently of the fact that you have or you haven´t to do the exam).

In addition I introduced the Master equation, the underlying idea of the Gillespie simulation scheme, and the resolution in terms of momenta by means of the characteristic function. In particular we solved the problem of a Brownian particle diffusing in a lattice and also the birth and death processes in a population where we saw that no matter that the average could grow exponentially the fate of the population actually depends on the initial condition since (again) fluctuation can be very important.

Class: December 5th 2007

In our first class about population dynamics we review Markov chains and applied this formalism to a simple approach to infection dynamics in a population. In addition we also applied this formalism to the analysis of ssDNA strands. There was some problems (my fault!) about the way I posed this particular problem. In order to clarify this issue please find HERE that problem solved.

GePasi Biochemical Simulation Suite

May be some of you become interested in implementing numerical simulations of chemical kinetics models. I strongly recommend that you try always to develop your own code. However, I also would like to let you know about the existence of simulation suites out there. In this regard, probably THE suite is GePasi (freeware). Enjoy.

PhD at Tarragona

PhD in statistical physics of polymers and membranes
Joint groups “Complex Systems” and “Polymers and Interfaces” of the ETSEQ at the University Rovira i Virgili of Tarragona Spain, are seeking a candidate for a 3 year PhD program. The selected candidate will integrate the research line on theoretical modelling of Drug Delivery systems to work on the development of the Single Chain Mean Field theory to discover the physical mechanisms of the
cytotoxicity.
Often the polymeric drug carriers in the assembled state are more toxic for cells than when in a dissociated state. The reasons of this significant increase of toxicity for the cell when assembled as well as the ways to reduce it are still unknown. Although the increased toxicity is sometimes attributed to the ability of the drug carriers to dissolve membrane lipids in the carrier cores, this remains as a speculative idea. During the contact with cell membranes the drug carriers may suck phospholipids and other constituents of cells into the cores, thus irreversibly damaging them. Hydrophobic polymers may precipitate onto and aggregate with the cell membrane forming pores that could be fatal for the cell.
The selected candidate will use the Self-Consistent Mean Field theory to describe the structures of membrane – polymer complexes in order to discover the mechanisms of the membrane disruption. The research will aim to find the way to control the cytotoxicity by adjusting the structure of the polymers used for concrete practical
applications. We seek a candidate with B.S. degree in Statistical physics with good knowledge of Theoretical physics and numerical methods and motivated to work in the field of soft matter physics, statistical physics of polymers and biophysics.
Further details are available from http://www.drugdelivery.front.ru/
Informal enquires (and applications) should be sent by e-mail to
Dr. Vladimir Baulin
Universitat Rovira i Virgili
Tarragona (Spain)
and
ICREA (Institució Catalana de Recerca i Estudis Avançats)
Passeig Lluís Companys, 23
08010 Barcelona (Spain)
e-mail: vladimir.baulin@urv.cat
Tel +34 977 55 85 77
Personal web page: http://vbaulin.front.ru/

Tutorial Class 31th, 17:00 ->18:00

The tutorial class that some of you demanded will take place on Wednesday 31th from 17:00 till 18:00 at conference room 507.

Second law violation

I have a question from the second law violation we saw the other day in class. Is it really a 2nd law violation? I think thermodynamics is a "macroscopic" science and has to be read in therms of a global well averaged quantities. In the case we studied in class the average of the dissipative work was allways positive, indeed in a big enough system we will find low-likely states in which the 2nd law is violated. So, is there really a violation of the second law? or is it simply a language abuse?

Class: October 17th 2007

In our last class for this block we addressed how important are fluctuations in Biophysics and how useful information can be obtained for them. Thus, we first reviewed the Brownian motion and the Perrin's estimation of the Avogadro number (Perrin's Nobel Lecture can be found HERE: at the Monomolecular Films section you'll find the experiment I told you about soup bubbles). We also saw in class how equilibrium properties can be obtained from irreversible processes. In this regard, we introduced the concept of dissipation and the so-called Crooks fluctuation theorem that revealed that 2nd law is in fact violated for some trajectories. That violation is evident as the number of thermodynamics microstates is "small". Biophysics problems are therefore a good candidate to show those violations and in fact ARN pulling experiments (among others) have shown that is the case. In our next block we will deal even more with fluctuations and learn how can be properly described.
P.S. PLEASE REMEMBER ABOUT YOUR HOMEWORK!!!, also...please complete the questionnaires.

Inequality...

Hi!

I commented with some of you that I was trying to prove the Onsager inequalty given in class, but I had some problems. Finally I found the mistake, if you are interested in the demonstration it is HERE. Carles commented that there is other easier way to demonstrate it by fixing one of the forces and solving the second equation taking the other force as the unknown quantity.

Hi everybody!

I found some interesting information about what I'm working with at the lab and I thougt that it could be interesting to tell you something about the subject and to give you some links, as well. The idea is: which is the role of integrins in neuronal migration? (We were talking about integrins and platelets).

The integrin beta1 is a transmembrane heterodimeric receptor that plays an important role in neuronal migration. This protein has many different functions related with the interaction between the cell and its environment. Yet there are two main ways in which this integrin is involved in neuron growth:

1. it is the one responsible for the attachment of the cell to the extracellular matrix,
2. and it also permits the cell to be continuously exploring its surrounding to 'decide' which path it has to follow to get the target.

Laminin is the ligand that binds to integrin to anchor the cell to the extracellular matrix (ECM). As Schmidt et al. could demonstrate in 1995, lamellipodia (leading edge) are the regions which contain the greatest concentration of integrins that exert a force over the substrate. This means that receptors located here are responsible for the traction force that enables neuron movement. Actin filaments push forward the cell membrane in a step-by-step manner due to the action of myosins (Kress et al. 2007), while integrins are being fixed to the substrate. Then, those which get the base of the growth cone are packaged by endocytosis and transported to the front once again, showing a periodic cicle similar to that of actin monomers (see figure). This agrees with the idea that integrins represent a physical bond between the cytoskeleton of the cell and the ECM.

On the other hand, this receptor has a second important function by enabling the neuron to stablish a communication with the environment. The concentration of ligands surrounding the neuron determine the way that the cell should take. So, integrins become, in that sense, the 'nose' of the neuron.

Problems with the RSS feed

I noticed that since the blog has a restricted access, the RSS feed is not working (at least for me with my web browser). Therefore, DO NOT trust the RSS feed for getting informed about when the blog has been updated. Unfortunately, I still don't know how to fix this problem: that is, keep an eye in the blog regularly.

More questions..

Thanks for your comments on my post, JB and Daniel. I see clearly the point you mention (one cannot apply the 2nd law to open systems such as living beings or the earth), but I keep on wondering what kind of system is the universe itself...In all our thermodynamical calculations, the universe is always considered as an isolated system, and that’s the reason why it is expected to end as a thermal soup, isn’t it? One of my questions is if it is possible to have ¿spontaneous? forces (and flows) in an isolated system... I would like to know an example of spontaneous macroscopic forces and flows in an isolated system. If there are no exchanges with the surroundings, where comes the energy from to drive changes? In other words, if the only natural state for an isolated system is that of maximal entropy, why the universe has not remained as an entropy soup from the very beginning?. It is difficult to imagine an isolated system that evolves to anything more organized...unless it starts to exchange heat, work, any kind of energy with the surroundings and hence, it is not isolated any more. The point is that isolated systems do not get organized with time, but become more and more “disordered“– or more exactly, evolve to states of maximum probability and multiplicity, the macrostates with the higher number of microstates or configurations available, is that right? Apparently the universe has not evolved in that sense: the old universe the infrarred techniques can detect seems a lot more homogeneous, disordered and probable that the one we can see today....Where’s the increasing entropy to satisfy the 2nd law? Another point is that to have organization one must be far from equilibrium, and one cannot maintain this state in an isolated system. Perhaps there is a lot of entropy in black holes, or other universes and big bangs as some hypothesis suggest...who knows. Anyway, if “The End” of all this is a boring thermal soup – or a big crunch...- it is even more amazing what thermodynamical laws heve been able to create in the middle...

I would like also to comment the integrins paper, and to ask about the phenomenon of entropy-enthalpy compensation that is mentioned by the authors. Years ago I read a paper that suggested the possibilty that the surprisingly good correlation that exists between entropy and enthalpy increase in some processes ( a plot of ∆S versus ∆H can give almost a straight line with a slope dependent on T, I think) could be a sign that we were measuring or observing the same physical variable from two different points of view..(I suppose, something like the particle-wave duality?). Anyone knows an explanation for this phenomenon, or is it just an artifact?

More comments on the blog

Arnau asked me today if (in addition to include comments to the post) you can post: YES, YOU CAN (and ideally you will). For posting you must access the blogger home page: follow THIS link. Just login with your gmail account and there you go. For those of you that already have a blog in blogger, once you access you will be able to choose the blog where you want to post to. Just one more thing, as I said the other day (see below) PLEASE USE THE TEMPLATE, DO NOT USE YOUR OWN, in this way you will be able to distinguish between posts that come from you from those that don't.

Class: October 15th 2007

Today we reviewed the paper about lambda phage. We derived all the modeling equations that lead to the behaviour of the cI/cro operon during lysogenic "life style". In addition we saw how the cannonical representation can be deduced from our previous knowledge and showed the repression curves of the PR and PRM promoters as a function of the total amount of repressor that is in the system. The calculation of these curves lies on the calculation of the Gibbs free energies and we saw that those energies can be computed by means of the wild-type and mutant experiments.
For those of you that are interested, in THIS link you will find a more detailed explanation about lambda phage (FLASH required).
Next day will be our last class for this block and we will see that non-equilibrium thermodynamics can be also very useful in biophysics....

Class: October 10th 2007

Today we first reviewed the paper about integrins. I tried to make you understand why integrin are important and, specially, why integrin clustering is relevant and worth to study. Thus, we reviewed the main results of the paper and showed that integrin clustering is driven by both ligand binding and temperature. We also saw how the knowledge that you got in class can be applied to real problems to calculate Gibbs energy, entalphy, and entropy changes. In the second part I introduced non-equilibrium thermodynamics in its simplest version: the linear approach (also known as linear response). We also reviewed the Prigogine theorem in regard of minimization of entropy production. Next day we will continue with non-equilibrium thermodynamics and we will check out the first paper (the lambda phage one).

P.S. Today you let me know that ONLY gmail accounts can access to the Blog: please get one account by following THIS link. Gmail is THE BEST on-line mail system, you won't regret getting that account. Please consider also subscribing to the feed (see my post on October 9th) to get informed about new posts in an automatic way without checking out the blog continuously. Starting tomorrow access to the blog will be restricted to those that have registered.

Some comments about the Blog

Finally we got our first post from one of you (students)!: thank you Laura (see below) . I just want to let you know several things about the Blog. In order to distinguish between posts the following images will be always used:

a) If the topic of the post is about a summary of our last class, I (JB) will use:

b) For other topics I (JB) will use:

c) As for your (students) posts, please note that when trying to post you reach a template: USE THAT TEMPLATE, DO NOT USE YOUR OWN TEMPLATE. In that way your (students) posts will be indicated by:

Finally, notice that for commenting on a particular entry (post) you must use the comments link by the end of any particular entry. On the other hand, at the very bottom of this page, just after the first post, you can find a link that states Subscribe to: Posts (Atom). Following this link you can subscribe to a feed that will inform you when new entries (posts) have appeared in the Blog.

A question from the biochemistry side...Is the entropy of the universe (really) increasing?

Hello everybody,

I would like to ask a rather philosophycal question...Let's see, from the biochemistry point of view, in order to develop some kind of complexity and self-organization, a system needs:

1- To be far from equilibrium: actually, equilibrium is death for a living system

2- To evolve to and maintain this (more or less) stationary state, the system has to decrease its entropy, at the same time increasing the entropy of the surroundings in order to satisfy the 2nd law (Overall, we have: system+surrounding=universe, considered an isolated system with increasing entropy)...

For a living system, that means to work as a so called dissipative structure, with a continuous flow of energy/entropy: the system takes energy (food) from the surroundings that allows it to maintain non-equilibrium states and make useful work (for example, to keep an electrochemical gradient across cell membrane, active transport, etc). On the other side, metabollic irreversible processes dissipate heat (entropy) in the surroundings - and when coupled to other processes, act as the driving forces of metabolism.

My question is as follows...what kind of system is the universe? By definition, the universe is an isolated system - if open, what are the surroundings for such a system ?? I mean, if the universe is an isolated system, could it be possible its self-organization according to the 2nd law?.. Is the universe a dissipative structure also? Is it possible to have inside an isolated system, flows of energy between different places, creating organization in certain spots and disorder=heat in the others?

In other words..Is the entropy of the universe increasing with time? Is that compatible with the trend to self-organization at all scales? I've always wondered about this question, since it's amazing the high degree of organization of the universe... galaxies, planets, living beings, cells, molecules...Will it be the final state of the universe an "entropy-soup"?

For a cell it would be impossible to maintain its organization as an isolated system..Even more, it would be impossible to develop the complexity of a cell from an isolated system.

Probably, these are rather obvious questions, but since I am not physicist it would be interesting to have some physical/thermodynamical insights.

By the way, as a biochemist I see no problem that during development the egg releases some heat...one can think this way: the first sign of death is that the body temperature reaches equilibrium with the surroundings...Both life and development are clearly irreversible phenomena. We create some amount of heat everyday as a result of metabollic irreversible processes, and one of the main concerns for a living being is how to dissipate that heat in order to keep an optimal temperature for biochemical reactions (thermoregulation). Actually we have specific mechanisms just to release heat by means of irreversible reactions in order to keep temperature, such as brown fat tissue. But that's another story..

Regarding to the question in this post, I've searched a little bit and it seems there are no definitive answers but hypothesis from black holes to multiple big-bangs... I add some sentences from an article suggesting the last idea - many big-bangs creating infinite entropy in an irreversible universe: "Regardless of the direction in which they run, the new universes created in these big bangs will continue the process of increasing entropy. In this never-ending cycle, the universe never achieves equilibrium. If it did achieve equilibrium, nothing would ever happen. There would be no arrow of time. " If someone feels curious: http://arxiv.org/abs/hep-th/0410270 . I hope you will find interesting the question. Many thanks!!

Class: October 8th 2007

Today we ended with our review of equilibirum thermodynamics. We introduced the concept of osmotic pressure and applied it to cell membranes. Moreover, our approach to that problem allowed us to introduce open systems. Thus, we saw how the free energy must be modified to include the contribution of mass changes. According to this we defined the so-called chemical potential. Equilibrium properties are related with the balances of the chemical potentials and this led us to the mass action law. In addition we discussed how equilibrium is reached and deduced the differential equations that govern that process. Finally, we discuss the concept of thermodynamic standard and concluded that in biophysics a standard that takes into account the fact that pH~7 must be defined: the biological standard. Unfortunately today we didn't (I didn't) have enough time to comment on the paper (the integrins one), we will do that in the next class on wednesday (READ IT, STUDY IT!!) and we will also start discussing (if we have time) non-equilibrium thermodynamis.

Class: October 3rd 2007

Today we started the classes of introduction to physics of biological system. As I commented on in class we will mostly deal with thermodynamics. We have reviewd some fundamentals of equilibrium thermodynamics including the 1st and 2nd principles, the concepts of thermodynamic potentials, importantly, the concept of thermal energy (4.1 pN.nm) that is perpetually surrounding and acting on biophysical systems. We also commented on the concept of spontaneous processes and learned (reviewed) that entropy increase is not in oposition to spontaneus processes. In fact I used the example of the chicken and the egg. In the following paper you can see some research on that topic:

Studies in the development of the rainbow trout: the heat production and nitrogenous excretion, S. Smith.


Next day we will comment on the integrin paper (READ IT!!, STUDY IT!!) and hopefully finish our equilibrium thermodynamic review.

Welcome: The rules!, and Introduction to physics of biological systems

Generalities

It is crucial that you provide me an email address for getting allowed to post in the blog. Only registered users can post in this blog.

General Biophysics

This subject is coordinated by Dr. Marta Ibañes (M.I.) and myself (Dr. Javier Buceta, J.B.). Both, together with Drs. Jose María Sancho (J.M.S.) and Ignasi Pagonabarraga (I.P.) are the lectures of this mandatory subject that is divided in different blocks. Each of us will be in charge of different parts in a coordinated way:

• Introduction to physics in biological systems (J.B.)
  
• Introduction to biology (M.I.)
  
• Biophysics at the molecular scale(J.M.S.)
  
• Biophysics at the cellular scale(I.P.)
  
• Biophysics of populations: stochastic methods (J.B.)
  
• Introduction to systems biology (M.I.)
  

May be some topics will appear "repeated" along the course. However, we will try to minimize redundancies and (when not possible) to focus on different aspects.

Articles

In regard of the blocks I'll teach, in each of them we will comment on different research articles. Those papers will be available for download from the blog. You MUST read and study those papers. Besides the homework you must present for the subject, continuous evaluation lies on the work you perform on those papers, class attendance (mandatory), questioning/discussion in class, and, in general, your active participation.

Homework

A short list of "easy" problems will be provided. This problems are not mandatory but a self-test. In addition, you must present a work (or works) that will be related to the papers we'll discuss in class. Although is not mandatory, I encourage you to use English both in class and in those works. Deadline for work presentation is before I start to teach the next block (December 3rd): no exceptions, no reminders!!!!. You must send me your homework via email. Homework will be available for download from the blog (see below). Work based on the research articles must preserve the style of a research article if indicated. The following structure must be followed (when possible):

• Abstract: a summary of the idea or ideas that you discuss in the work and the main results and conclusions (~150 words max.).
  
• Introduction: motivation and relevant questions to discuss and solve(~1000 words max.).
  
• Methods: tools (theoretical and numerical) you used to solve your work (~500 words max.).
  
• Results: results of the work and answer to the questions provided (if any).
  
• Conclusions and discussion: main conclusions of the work, possible extensions, criticisms, limitations....(~500 words max.).
  
• References: bibliography.
  
• Supplementary material: if you consider that additional information must be provided this is the section where you can do it.

Introduction to physics in biological systems


This is the first block I'll teach for the subject of General Biophysics. It is divided in 5 classes during October (5th, 8th, 10th, 15th, and 17th) from 11:50 to 13:40. This block will be mostly focused on thermodynamics applied to biological problems from the point of view of Chemical-Physics:

• Thermodynamics reminder
  
• Introduction to kinetic theory
  
• Thermodynamic potentials
  
• Mass-action law
  
• Introduction to non-equilibrium thermodynamics
  

Research articles for this block are ("click" to download, PDF format):

• Quantitative Model for Gene Regulation by lambda phage repressor, G.K. Ackers et al., PNAS 79, 1129 (1982).
• Ligand Binding Promotes the Entropy-driven Oligomerization of Integrin alpha IIb Beta 3, R.R. Hantgan et al., J. Bio. Chem. 278, 3417 (2003).
  

Homework for this block:

• Homework 1 (present in article style)
  
• Homework 2 (no article style is required)
  

In addition, HERE you can download three simple problems of thermodynamics. If you have troubles solving these problems you surely need to study thermodynamics urgently. Another biological self-test: can you identify the different cellular processes that appear in this wonderful animation?. Probably you don't: no panic, by the end of the master you'll be able to.>
Finally, some bibliography:

• Physical-chemistry for the Life Sciences by Atkins and Paula
  


• Biological physics by Nelson
  


• Temas de biofisica by Buceta et al.