Can self-assembling molecules show us how cells function?

  • Thread starter Thread starter Diderot
  • Start date Start date
  • Tags Tags
    Cell Picture
AI Thread Summary
Self-assembling molecules within cells exhibit chaotic movement, with small molecules traveling at speeds up to 250 miles per hour and proteins tumbling at a million times per second. This high-speed motion is typical at the molecular scale and is essential for cellular function, allowing molecules to frequently encounter one another by chance. While some argue that this randomness could hinder assembly, it is clarified that molecular interactions are governed by thermodynamics and chemical properties, leading to organized structures despite the chaos. Active transport mechanisms, such as those involving the cytoskeleton, also play a crucial role in directing proteins to specific locations within the cell. Overall, the dynamic environment of the cell is a complex interplay of rapid motion and organized biochemical processes.
  • #51
"The essence of cellular life is regulation: The cell controls how much and what kinds of chemicals it makes; when it loses control, it dies."
In respect to the demand for fine-tuned regulation I'm still struggling with the concept of diffusion as a transport system.
Darwin123 said:
Physicists and biologists think of diffusion as one specific type of transport. ... Diffusion is the transport that is characterized by "random" motions of the molecules. [D]iffusion dominates within an organelle.
Earlier in this thread I wrote:
Diderot said:
I'm trying to incorporate these speeds in my understanding of the cell. According to Ken Shirrif these speeds explain a lot: “Watching the video, you might wonder how the different pieces just happen to move to the right place. In reality, they are covering so much ground in the cell so fast that they will be in the ‘right place’ very frequently just by chance.” This seems debatable to me. If in a workshop all the parts of a car are floating around it’s hard to imagine that a car will be assembled. ...
Simon Bridge said:
[T]hough everything is moving fast, the interactions are even faster. On top of that, the different bits have a range of ways they attract and repel other bits...
If the different bits have the possibility to form all sorts of chemical bonds the only result can be chaos. Random movement of Lego parts cannot explain a complex Lego car. So the different bits must all be highly specified and have just one possibility to fall into place.
Simon Bridge said:
To use your analogy of car assembly - it's like the situation where different workers and parts arrive at different times ... when someone sees the right part, they put it in the car. You can build a car that way - in fact, hobby auto-mechanics (restoring a car for eg) often works like that...
Another thing that is necessary is sequence of assembly. So highly specified part A must have just one possibility B at moment C and highly specified part A’ must have just one possibility B’ at moment C’ … etc.

What do you think? Am I getting closer to understanding?
 
Biology news on Phys.org
  • #52
Diderot said:
If the different bits have the possibility to form all sorts of chemical bonds the only result can be chaos. Random movement of Lego parts cannot explain a complex Lego car. So the different bits must all be highly specified and have just one possibility to fall into place.
A quick piece of advice; when learning about a topic it is best to not making conclusions that contradict what is already known. It doesn't give the impression of a good attitude for learning and in the case of something relevant to evolution may get you branded as a creationist with an agenda.

Whilst many molecules such as proteins have multiple roles they generally have very specific active sites. With regards to assembly look into chaperone proteins.
 
  • #53
Ryan_m_b said:
A quick piece of advice; when learning about a topic it is best to not making conclusions that contradict what is already known. It doesn't give the impression of a good attitude for learning and in the case of something relevant to evolution may get you branded as a creationist with an agenda.
Whilst many molecules such as proteins have multiple roles they generally have very specific active sites. With regards to assembly look into chaperone proteins.
First of all, please excuse me for my bad English writing. It is not my intention to make a creationist point here. I'm trying to imagine how diffusion can contribute to order. All sorts of possibilities for chemical bonds seemed like an obvious threat to order to me, so I’m arguing for highly specified parts that can fall in their unique places in a specific sequence.
Unfortunately my knowledge of biology is also extremely poor so it’s no surprise that my statements contradict what is already known.
I would appreciate it very much if someone points out where I go wrong.
 
  • #54
Diderot said:
First of all, please excuse me for my bad English writing. It is not my intention to make a creationist point here. I'm trying to imagine how diffusion can contribute to order. All sorts of possibilities for chemical bonds seemed like an obvious threat to order to me, so I’m arguing for highly specified parts that can fall in their unique places in a specific sequence.
Unfortunately my knowledge of biology is also extremely poor so it’s no surprise that my statements contradict what is already known.
I would appreciate it very much if someone points out where I go wrong.
I am not sure what you are asking. The way you write English makes it appear as though you are pointing out something you think is wrong. I don't really know what issues to address.
One problem with the English is that you are excessively anthropomorphizing everything. For instance, you say that "all sorts of possibilities for chemical bonds seems like an obvious threat to order to me." Are the chemical bonds really threatening order? Is it obvious that the chemical bonds are threatening? Furthermore, you are "trying to imagine how diffusion can contribute to order." Did anyone say "diffusion is contributing to order"? You seem to think that diffusion is countering the threat of the possible chemical bonds.
Maybe you are asking what reduces the probability of most chemical bonds forming, and why some chemical bonds are likely to form anyway. With that:
In what are called living things, there are these large molecules with specific shapes. This simplified model is called "lock and key theory." The shape of the molecule makes certain chemical bonds unlikely to form after collision with other molecules. The shape of the molecule allows certain bonds to for after collision with other molecules.
The selectivity is 80% of the time determined just by the geometry (shape) of the molecule. There are also electrical and magnetic forces involved. Quantum mechanics is also involved. What is important is that some chemical reactions are more likely than others for certain molecules. I will dump all these different properties into the word "shape". The randomness of the collision is greatly reduced by the shape and properties of the molecules.
Now, maybe you want to know how the shape of the molecule got that way.
The shape of each molecule is copied with high fidelity from generation to generation. However, high fidelity doesn't mean infinite fidelity. Some cells in each generation have a molecule or two which is slightly different. These are called inherited variations. Most mutations increase the probability of the cell dying or not reproducing in a certain environment. Some inherited variations improve the probability of the cell dying out in that environment. The cells with the improvements eventually outnumber the ones that remained the same or decreased the chance of survival. This is natural selection.
Natural selection together with inherited variation supposedly determined the current shape of the molecules. Hypothetically, the molecules in the first generations of life did not have the specific shapes they had now. However, generation after generation of variation and selection has resulted in molecules of very specific shape.
Now, what in my description can't you imagine?
There was an article in the Washington Post on 20 September 2012 (Wedsday) in the Politics and Nation section. Some scientists kept a colony in a bacteria (E. coli) in bottle for 25 years. This corresponds to 50,000 generations of bacteria. The PI was Richard Lenski of Michigan State University. The full experiment is described in a recent issue of Nature. Alas, I don't have the original article in Nature.
Every 500 generations, a sample from the colony was frozen as a record of changes. Some challenge was given every day to the flask. Every day, part of the colony was transferred to a new sugar solution. However, there was no exotic manipulation of the bacteria.
The bacteria in the flask now have different molecules and different chemical reaction chains then their distant ancestors.
The current bacteria now can digest citrate, something their distant ancestors could not do. This took about 30,000 generations of bacteria. Some of these chemical reaction chains seem very specific and rather complex.
Yet at no time did any scientist "design" the molecules or reactions. The shape was not directly controlled except by providing that very general "challenge". There was no guidance to the shape. They just moved the bacteria into a new flask with fresh sugar every day. Yet, the new molecules have to have a really complex and specific shape to digest citrate. There are several other "unlikely" changes that have occurred over the 50,000 generations.
Now, what do you think happened in that flask over 25 years and 50,000 generations?
Please answer without anthropomorphizing anything. The E. coli may be insulted.
 
  • #55
Diderot said:
If the different bits have the possibility to form all sorts of chemical bonds the only result can be chaos. Random movement of Lego parts cannot explain a complex Lego car. So the different bits must all be highly specified and have just one possibility to fall into place.

Another thing that is necessary is sequence of assembly. So highly specified part A must have just one possibility B at moment C and highly specified part A’ must have just one possibility B’ at moment C’ … etc.

Yes, this is essentially correct. There are also various ways of preventing and undoing errors.
http://www.ncbi.nlm.nih.gov/books/NBK26850/
http://www.ncbi.nlm.nih.gov/books/NBK26829/
http://en.wikipedia.org/wiki/Kinetic_proofreading
 
  • #56
Diderot said:
If the different bits have the possibility to form all sorts of chemical bonds the only result can be chaos. Random movement of Lego parts cannot explain a complex Lego car. So the different bits must all be highly specified and have just one possibility to fall into place.
This, I think, is the problem statement (especially in the context of your quotes). In the first place, Legos are a bad example because they have very limited degrees of freedom for coupling (there's very few ways you can put Legos together). The building blocks of life, on the other hand, are rather "sticky" (they stick together in all kinds of different ways).

But more importantly, your statement opposes the view that these sticky pieces can, indeed, through random motion, form functional structures. You have to remember the age of Earth and how many chances it's had to perform random trials. Even with legos, if you jumble them around in a box enough times, there is a chance they will eventually make some simple structures (even a car, though the chance is very very low). In none of these examples would you be able to commit enough trials in your lifetime... but life exceeds many lifetimes; billions of years of trials. It's not really surprising that all these sticky components had a chance to stick together in complicated ways.

And remember that they didn't start out quite as complicated, it's been a very long period of emergence. There's a point at which early Earth chemistry becomes "life" through these small, random changes. Self-organized complexity.

Here's a very simple example:

KPP-4-LEHXQ[/youtube] notice that ... heat vents, the lipid layer, and the ocean.)
 
  • #57
Have fun :biggrin:

http://www.sigmaaldrich.com/etc/medialib/docs/Sigma-Aldrich/General_Information/metabolicpathways_updated_02_07.Par.0001.File.tmp/metabolic_pathways_poster.pdf
 
  • #58
Pythagorean said:
This, I think, is the problem statement (especially in the context of your quotes). In the first place, Legos are a bad example because they have very limited degrees of freedom for coupling (there's very few ways you can put Legos together). The building blocks of life, on the other hand, are rather "sticky" (they stick together in all kinds of different ways).

But more importantly, your statement opposes the view that these sticky pieces can, indeed, through random motion, form functional structures. You have to remember the age of Earth and how many chances it's had to perform random trials. Even with legos, if you jumble them around in a box enough times, there is a chance they will eventually make some simple structures (even a car, though the chance is very very low). In none of these examples would you be able to commit enough trials in your lifetime... but life exceeds many lifetimes; billions of years of trials. It's not really surprising that all these sticky components had a chance to stick together in complicated ways.

And remember that they didn't start out quite as complicated, it's been a very long period of emergence. There's a point at which early Earth chemistry becomes "life" through these small, random changes. Self-organized complexity.

Here's a very simple example:

KPP-4-LEHXQ[/youtube] notice tha...gent laws that are essentially deterministic.
 
  • #59
atyy said:
Could you also address that "random" may mean essentially deterministic? For example, can the second law of thermodynamics be violated? Theoretically yes, practically no. So it would not be wrong to say that there are emergent laws that are essentially deterministic.

When I use random in this context, I mean in the noise sense. We can use a random distribution to model noise, but the noise could have easily come from several unrelated deterministic processes. The "random" terminology illustrates that aspect: that the sources are uncorrelated.
 
  • #60
Pythagorean said:
When I use random in this context, I mean in the noise sense. We can use a random distribution to model noise, but the noise could have easily come from several unrelated deterministic processes. The "random" terminology illustrates that aspect: that the sources are uncorrelated.

Hmmm, would "1/f noise" be noise then, since it would have correlations on all time scales?
 
  • #61
Diderot said:
Is it fair to say that there is a very 'delicate balance' between all the chemical reactions in the cell? There must be an exact amount of everything?
No, not all chemical reactions, No, there doesn't have to be an "exact" amount of everything. Obviously, there is a great amount of variation in the amounts of different chemicals in the body.
Diderot said:
The smallest change (mutation) can destroy this balance, and shatter the coincidental cooperation of the parts?
No. Small mutations do not destroy the balance. Obviously, there is a lot of variation within a species and even in an individual. Obviously, small variations in chemistry don't shatter the "coincidental" cooperation of parts. Mind you, I don't know what you mean by coincidental.
Diderot said:
And is it fair to say that this balance is unsupported?
Yes. I think so. I don't know what you mean by unsupported. However, there are a lot of people who have hypothesized that life is unsupported. As Job said, the foundations of the Earth are not supported !-)
Diderot said:
Nothing is 'interested' in keeping this delicate balance; not the parts of the cell, not the surroundings of the cell and not the cell itself?
If you mean conscious interest, then no.
The statistics of "natural selection" can be said to support any balance there is, delicate or not.
 
  • #62
Darwin123 said:
One problem with the English is that you are excessively anthropomorphizing everything. For instance, you say that "all sorts of possibilities for chemical bonds seems like an obvious threat to order to me." Are the chemical bonds really threatening order? Is it obvious that the chemical bonds are threatening?
There is a language barrier here, due to my poor English of course, but I will try my utmost to be clear. I’m thinking of the car workshop where all the parts of a car are floating around (diffusion) and ‘miraculously’ fall into the right place and so build a car. Out of chaos comes order. To explain this ‘miracle’ I think we must assume that every piece has a right place to fall into. Maybe some parts have multiple right places, but If the driving wheel also fit on the bumper and on the headlights it will have a negative impact on the probability that the car can be assembled by diffusion. This is what I meant when I said: "all sorts of possibilities for chemical bonds seems like an obvious threat to order to me”. I understand that my choice for ‘threat’ is clumsy; maybe I should have said ‘problem’? By ‘order’ I mean the correct assembling of the car.
So to explain the ‘miracle’ of assembling by diffusion we need parts with specific shapes otherwise there is no 'falling into its right place'. This http://www.pnas.org/content/suppl/2007/12/05/0709489104.DC1/09489Movie2.mov gives a very simple example of ‘falling into its right place’:

Every part is falling into its right place. Unfortunately the parts in the movie all have the same shape which seems to contradict my reasoning. But I don’t think it does.
Darwin123 said:
This simplified model is called "lock and key theory." The shape of the molecule makes certain chemical bonds unlikely to form after collision with other molecules.
“Lock and key theory”, I like that analogy. Thank you, I will study this.
I also think that there has to be a sequence in the assembling of the car. So highly specified part A must have just one right place B at moment C and highly specified part A’ must have just one right place B’ at moment C’ … etc.
The parts in the cell are like pieces of an constantly changing puzzle.
Darwin123 said:
The way you write English makes it appear as though you are pointing out something you think is wrong.
I do have a problem understanding it. For me this is not so simple.
 
  • #63
atyy said:
Hmmm, would "1/f noise" be noise then, since it would have correlations on all time scales?

I typed up a big response, then realized it was kind of derailing, so I tried to pm you my response, but you don't have pm set up, but I guess the bottom line is that a lot of metaphysics come into play.

I'm also imaging a statespace bigger than just time; spatial correlation is just as important as temporal correlation. Sometimes 1/f dependency is happenstance too (as an over-simplified example, big waves travel further than little waves, so sampling ambient acoustics might yield pink noise, you'll be getting more global data in low frequencies and more local data in higher frequencies; once you adjust your system a posteriori for that bias, you have white noise again.)
 
  • #64
Darwin123 said:
The current bacteria now can digest citrate, something their distant ancestors could not do.

How did they test for the distant ancestors not having this ability at a low level?
 
  • #65
Pythagorean said:
I typed up a big response, then realized it was kind of derailing, so I tried to pm you my response, but you don't have pm set up, but I guess the bottom line is that a lot of metaphysics come into play.

I'm also imaging a statespace bigger than just time; spatial correlation is just as important as temporal correlation. Sometimes 1/f dependency is happenstance too (as an over-simplified example, big waves travel further than little waves, so sampling ambient acoustics might yield pink noise, you'll be getting more global data in low frequencies and more local data in higher frequencies; once you adjust your system a posteriori for that bias, you have white noise again.)

If whether a process is random or not by your definition (zero correlations) depends on a prior, then isn't it subjective? Consequently, couldn't the OP's use of "random" be justified under a different prior? To go back to the example of entropy - I don't think it is misleading to say that entropy always increases, although strictly speaking that seems to be only a probabilistic law. Similarly, we can predict using free energies what reactions will occur in cells, even though we are only using thermodynamics. Let me try to use your language: couldn't a non-flat free energy landscape be considered non-random, relative to a "flat" prior? In my language, I would say that macroscopic deterministic laws can emerge from random processes. So a clarification of the OP's question would not necessarily involve negation, but the statement of specific probability models and the relations between them, macroscopic and microscopic observables, error bounds, and regimes of validity.
 
Last edited:
  • #66
Ryan_m_b said:
A quick piece of advice; when learning about a topic it is best to not making conclusions that contradict what is already known. It doesn't give the impression of a good attitude for learning and in the case of something relevant to evolution may get you branded as a creationist with an agenda.

Whilst many molecules such as proteins have multiple roles they generally have very specific active sites. With regards to assembly look into chaperone proteins.

I don't think one has to have a "creationist agenda" to ask such a question. The question is very similar to "Levinthal's paradox".

http://chemistry.caltech.edu/courses/ch110/lecture3.pdf
 
Last edited by a moderator:
  • #67
Diderot said:
If the different bits have the possibility to form all sorts of chemical bonds the only result can be chaos. Random movement of Lego parts cannot explain a complex Lego car. So the different bits must all be highly specified and have just one possibility to fall into place.

Actually, this is demonstrably false. The chemical and physical principles underlying self-assembly in biological systems are well understood and many experiments have demonstrated the ability of highly ordered structures to arise from random (Brownian) motion. Of course, the formation of these ordered structures do not violate the second law of thermodynamics; their formation is driven by binding interactions that convert chemical potential energy into heat, thereby counteracting the entropy lost by ordering the individual components into an assembly.

Here's a paper (citaiton below) on this topic that you may be interested in taking a look at. The paper describes various chemical systems that mimic the self-assembly of the icosahedral poliovirus capsid. Of particular interest, the authors constructed a toy capsid that self assembles when shaken in a container:

"By appropriate placement of oriented magnets as analogs to the electrostatic complementarity, we produced a model that mimics the self-assembly of the [poliovirus] from twelve pentameric assembly intermediates. Placing 12 of these tiles in a container and shaking with the appropriate strength results in a stable closed shell, usually within 1–2 min. The key aspects of this model were the fivefold symmetric tiles, the appropriate curvature at the tile interfaces, and the geometric and magnetic complementarity of the interfaces. Although intellectually we knew that this type of self-organization occurs spontaneously, watching it happen from random shaking on the macroscopic scale was inspirational."

The videos of the process (freely available http://www.pnas.org/content/suppl/2007/12/05/0709489104.DC1/09489Movie1.mov, and http://www.pnas.org/content/suppl/2007/12/05/0709489104.DC1/09489Movie2.mov) are, as the authors say, inspirational. Movie 2 is especially impressive because it shows that two different capsids (colored red and green) with the same shapes but reversed magnet polarity can self-assemble in the presence of each other without the formation of misfolded states. So yes, you can put a collection of lego-like bricks in a tube, shake it up, and get a complex self-assembled structure.

You can access the full paper at the PNAS website for free by following the link below:
Olson, Hu, and Keinan. 2007. Chemical mimicry of viral capsid self-assembly. Proc. Natl. Acad. Sci. USA 104: 20731-20736. http://dx.doi.org/10.1073/pnas.0709489104.On the topic of "delicate balance" and homeostasis, there is a good amount of scientific literature that has explored the effect of stochastic noise in protein and mRNA levels on the regulation of biological processes. I'll have to look up some good papers later, but Jonathan Weissman at UCSF and Erin O'Shea, formerly at UCSF now at Harvard, are two scientists who have done some of the key studies in this area. There's even an example of how bacteria take advantage of stochastic noise in order to produce pheotypic variability in a population of genetically identical cells (http://www.ncbi.nlm.nih.gov/pubmed/18927393).
 
Last edited:
  • #68
atyy said:
If whether a process is random or not by your definition (zero correlations) depends on a prior, then isn't it subjective? Consequently, couldn't the OP's use of "random" be justified under a different prior? To go back to the example of entropy - I don't think it is misleading to say that entropy always increases, although strictly speaking that seems to be only a probabilistic law. Similarly, we can predict using free energies what reactions will occur in cells, even though we are only using thermodynamics. Let me try to use your language: couldn't a non-flat free energy landscape be considered non-random, relative to a "flat" prior? In my language, I would say that macroscopic deterministic laws can emerge from random processes. So a clarification of the OP's question would not necessarily involve negation, but the statement of specific probability models and the relations between them, macroscopic and microscopic observables, error bounds, and regimes of validity.

Many things in science are subjective. We arbitrarily draw lines in a continuous spectrum. We can't prove a negative, but we'll take it for granted if we haven't proved its positive after several attempts.

The point is simply that there's not a master control system guiding each process. In the context of previous posts by the OP (some of which have been deleted) there seems to be an agenda for strong emergence (not particularly creationism). Perhaps it's all a big misunderstanding, but it's not getting cleared up in the month it's been shrinking in growing in size as posts are deleted and reworded.

What you seem to be proposing is weak emergence, which doesn't seem contradictory to my point. Whether you want to call consistent trends that emerge in the macroscopic world "laws" or not is not going to affect the science itself, it's just going to affect what aspects of the science you're emphasizing. So different research approaches are going to treat entropy differently. As long as we accept the map is not the territory, than we have to accept degeneracy between maps and territory. Some maps are going to describe different components differently. The strong emergence map doesn't tell you anything about the territory (except maybe hic sunt dracones).
 
  • #69
Given that the OP has admitted to a problematic language barrier and is trying to fill in some understanding of the basics could we please avoid going too off topic on discussions of what counts as random and subjectivity in the scientific method? This is not intended as a criticism but a friendly reminder that we must tailor our discussions to the understanding of the OP.
 
  • #70
Ygggdrasil said:
"By appropriate placement of oriented magnets as analogs to the electrostatic complementarity, we produced a model that mimics the self-assembly of the [poliovirus] from twelve pentameric assembly intermediates. Placing 12 of these tiles in a container and shaking with the appropriate strength results in a stable closed shell, usually within 1–2 min. The key aspects of this model were the fivefold symmetric tiles, the appropriate curvature at the tile interfaces, and the geometric and magnetic complementarity of the interfaces. Although intellectually we knew that this type of self-organization occurs spontaneously, watching it happen from random shaking on the macroscopic scale was inspirational."

Doesn't having to shake with "the appropriate strength" indicate a requirement for tuning?
 
  • #71
atyy said:
Doesn't having to shake with "the appropriate strength" indicate a requirement for tuning?
Certainly not "fine-tuning". There is a wide range of strengths that are appropriate. It isn't like the strength of shaking has to be correct within 0.01%. In fact, there is probably at least a magnitude of shaking strengths that would come up with the same type of order.
 
  • #72
atyy said:
Doesn't having to shake with "the appropriate strength" indicate a requirement for tuning?

Yes. Obviously if you shake hard enough, you will break apart any correctly assembled capsids that form, and if you do not shake hard enough, you won't be able to break apart any incorrectly assembled capsids. Although I have not played with the model described in the paper, I would assume that there is a fairly good range of shaking strengths over which you can form the capsid assemblies, however.

In the model, the strength of the shaking represents the amount of thermal energy in the environment surrounding the poliovirus capsid molecules (i.e. the temperature). Evolution tunes the strength of the intermolecular interactions between the capsid molecules such that the capsid molecules can assemble at that temperature (in the case of poliovirus, 37oC, the temperature of its host). It is well established that microevolutionary processes can select for amino acid mutations that tune protein-protein interactions for certain temperatures, and many experiments have demonstrated this principle.
 
  • #73
Ryan_m_b said:
Given that the OP has admitted to a problematic language barrier and is trying to fill in some understanding of the basics could we please avoid going too off topic on discussions of what counts as random and subjectivity in the scientific method? This is not intended as a criticism but a friendly reminder that we must tailor our discussions to the understanding of the OP.

The discussion of what is random can't be avoided. The meaning of the word "random" as used by scientists is crucial to the issue. The OP admits to having a language problem. However, a large part of the language problem is understanding how the motion of molecules can be said to be "random".
The OP appears to be interpreting the word "random" differently from scientists and most of the replies. It is not entirely clear what the OP thinks is meant by the word random. Scientists use the word random very differently. To be fair, even scientific usage of the word random varies.
I agree that subjectivity in science is not the issue here. Whether or not the scientists are subjective or objective is an unrelated issue. The concepts of subjectivity and objectivity have nothing to do with the concept of random. Subjectivity and objectivity are certainly interesting concepts that should be discussed in a different thread.
The way a scientist uses the word, "random" has nothing to do with either "consciousness", "causality" or even "programming". The OP has used all these words in conjunction with the word "random". Therefore, discussion of the word "random" is salient to the topic.
 
  • #74
Darwin123 said:
The discussion of what is random can't be avoided. The meaning of the word "random" as used by scientists is crucial to the issue. The OP admits to having a language problem. However, a large part of the language problem is understanding how the motion of molecules can be said to be "random".
The OP appears to be interpreting the word "random" differently from scientists and most of the replies. It is not entirely clear what the OP thinks is meant by the word random. Scientists use the word random very differently. To be fair, even scientific usage of the word random varies.
I agree that subjectivity in science is not the issue here. Whether or not the scientists are subjective or objective is an unrelated issue. The concepts of subjectivity and objectivity have nothing to do with the concept of random. Subjectivity and objectivity are certainly interesting concepts that should be discussed in a different thread.
The way a scientist uses the word, "random" has nothing to do with either "consciousness", "causality" or even "programming". The OP has used all these words in conjunction with the word "random". Therefore, discussion of the word "random" is salient to the topic.
I was not at all suggesting that the discussion was without merit nor that it shouldn't be had. I was trying to remind members to take into consideration the level of knowledge and language issues of the person they are trying to teach. By all means have the discussion but keep it to a level that is accessable and don't stray too far along it leaving the OP behind.
 
  • #75
- About diffusion as a transport mechanism -
Earlier I wrote: “So the different bits must all be highly specified and have just one possibility to fall into place”. This is in line with the ‘lock and key theory’; mentioned by Darwin123. However in case of multiple identical locks and keys, there are also multiple places (locks) for the individual keys and vice versa.

The lock and key theory is not applicable to the phenomenon of 'self-assembly' of identical parts into ordered structures, because all the particles are identical. The emergence of these ordered structures must be explained by the tendency of parts to form the most stable structure when under pressure from Brownian motion (or when being shaken as in the movie).

Both Pythagorean and Ygggdrasil criticize my statement "Random movement of Lego parts cannot explain a complex Lego car" and both point towards the phenomenon of self-assembly. They are right if a complex Lego car is indeed the most stable structure that Lego parts can form under pressure from Brownian motion. It is not apparent however that this is the case. A ball-like structure seems more likely.
 
  • #76
I would like to make some general points.

1. "Random" is a dangerous word. It is ambiguous without careful definition. An exposition at an elementary level is given in Chapter 21, "Probability and Ambiguity" of Martin Gardner's book. Consequently, one may get into arguments about whether something is random or not, simply by having different definitions of random. Such arguments are purely semantic, and not very meaningful.

2. One of the questions of the OP is closely related to Levinthal's paradox - if a protein folds "randomly", it will take longer than the lifetime of the universe to reach the observed conformation.

The resolution is of course to ask - what is the definition of "random" consistent with the laws of physics to use in this case? One hypothesis is to use a definition of randomness that includes a "bias". Because of the randomness and the bias, protein folding can be described as random and as directed, without contradiction.

http://www.phas.ubc.ca/~steve/publication/PlotkinOnuchic_part1_QRB02.pdf
http://www.haverford.edu/biology/Courses/Bio303/rf_bio303_dill.pdf
http://people.virginia.edu/~dta4n/biochem503/ProteinFoldingIandII.pdf
 
Last edited by a moderator:
  • #77
Diderot said:
Both Pythagorean and Ygggdrasil criticize my statement "Random movement of Lego parts cannot explain a complex Lego car" and both point towards the phenomenon of self-assembly. They are right if a complex Lego car is indeed the most stable structure that Lego parts can form under pressure from Brownian motion. It is not apparent however that this is the case. A ball-like structure seems more likely.

This has more to do with the inadequacies of your analogy (such basic analogies can only be carried so far). And the "most stable structure" isn't the right case for self-assembly. It's the path of least action, that doesn't always lead to the most stable structure for all time. The dynamics are important.

Lock-and-key is a simplification that helps in understanding of basic protein interaction, but it's by no means the whole story:

Choi said:
The activity of most proteins is critically dependent on attaining a unique tertiary structure that can position key amino acid residues for molecular recognition and catalysis. However, upwards of 30% of eukaryotic cellular proteins are predicted to be completely or partially intrinsically disordered (ID) (Uversky and Dunker, 2010). These intrinsically disordered proteins (IDPs) are critical for a variety of essential cellular functions like transcription, gating the nuclear pore and membrane fusion.

Despite lacking the “lock and key” interfaces of folded proteins, ID regions often contain sites of molecular recognition, even in proteins that also contain folded domains (Lee et al., 2000). Disorder has been proposed to enable two modes of ligand recognition: 1) ligand induced folding (Dyson and Wright, 2002), in which the IDP adopts a complementary interface after the initial ligand contact and 2) conformational selection (Tsai et al., 2001), in which binding occurs only if the binding site is preformed or unoccluded before ligand contact. These two binding modes depend differently on the timescale of conformational fluctuation within the IDP. Ligand induced folding necessitates fast structural transitions or ligands will diffuse away before the binding interface is formed (Zhou, 2010). To date there have been no physical measurements to support such differences in IDP conformational dynamics.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3075556/
 
  • #78
Pythagorean said:
This has more to do with the inadequacies of your analogy (such basic analogies can only be carried so far).
To what do you think my analogy is referring?
 
  • #79
Diderot said:
One could say that amidst the chaos created by diffusion the 'program of the cell' is being executed. So one could say that this program is offering 'guidance' to the parts in order to maintain the delicate balance of the cell.

Pythagorean said:
Probably not... unless the program is the laws of physics itself, in which case everything runs under its guidance. We generally accept some sort of anthropic principle. That is, the components of the cell work together so nicely simply because that combination of matter happened to work out so nicely. It's not a very satisfactory explanation to the human mind, but it's basically the idea behind selection, which is "half" of evolution (the other "half" being random mutation).

What about the use of the term "program" in
http://www.ncbi.nlm.nih.gov/pubmed/9576829
http://www.ncbi.nlm.nih.gov/pubmed/9115207
http://www.ncbi.nlm.nih.gov/pubmed/19269364
http://www.ncbi.nlm.nih.gov/pubmed/20054295
http://www.ncbi.nlm.nih.gov/pubmed/18555777 ?
 
Last edited:
  • #80
Diderot said:
To what do you think my analogy is referring?

cellular processes, what else?

atyy said:
What about the use of the term "program" in

Diderot was explicitly referring to the "program of the cell". Program is somewhat acceptable for cellular processes that rely strictly on a series of genetic "instructions", but to what extent are even these subcellular processes the result of emergent physics? Only the microstructures themselves are a result of a "program" (the genes: the list of instructions). A lot of it is emergent, such as the dynamics and the macrostructures.

And of course, the programs anyway, are a result of physics of long temporal scales. We isolate a particular set of molecules and the way they interact and call it a program, but it's a goal-oriented program like a software engineer would write.
 
  • #81
Pythagorean said:
Diderot was explicitly referring to the "program of the cell". Program is somewhat acceptable for cellular processes that rely strictly on a series of genetic "instructions", but to what extent are even these subcellular processes the result of emergent physics? Only the microstructures themselves are a result of a "program" (the genes: the list of instructions). A lot of it is emergent, such as the dynamics and the macrostructures.

Somewhat acceptable? I can find many more references. Those I gave you include "Cell" and "Nature". Not that the results have to be correct, but I would imagine they indicate very acceptable usage. Here are more examples, where it is used in "homeostatic program".

http://www.ncbi.nlm.nih.gov/pubmed/17113390
http://www.ncbi.nlm.nih.gov/pubmed/22053049
http://www.ncbi.nlm.nih.gov/pubmed/19594634

Edit: Here's another example "Checkpoints are comparable to the program in a washing machine that checks if one step has been properly completed before the next can start. Checkpoint defects are considered to be one of the reasons behind the transformation of normal cells into cancer cells." http://www.nobelprize.org/nobel_prizes/medicine/laureates/2001/presentation-speech.html
 
Last edited:
  • #82
Regardless, there's no "program of the cell".
 
  • #83
Diderot said:
- About diffusion as a transport mechanism -
Earlier I wrote: “So the different bits must all be highly specified and have just one possibility to fall into place”. This is in line with the ‘lock and key theory’; mentioned by Darwin123. However in case of multiple identical locks and keys, there are also multiple places (locks) for the individual keys and vice versa.

The lock and key theory is not applicable to the phenomenon of 'self-assembly' of identical parts into ordered structures, because all the particles are identical. The emergence of these ordered structures must be explained by the tendency of parts to form the most stable structure when under pressure from Brownian motion (or when being shaken as in the movie).

Both Pythagorean and Ygggdrasil criticize my statement "Random movement of Lego parts cannot explain a complex Lego car" and both point towards the phenomenon of self-assembly. They are right if a complex Lego car is indeed the most stable structure that Lego parts can form under pressure from Brownian motion. It is not apparent however that this is the case. A ball-like structure seems more likely.

Yes, you are essentially correct. Self-assembly will not work unless it is driven by the conversion of chemical potential energy into heat. That said, protein-protein interactions are driven by these forces, which explains how exothermic binding reactions can drive the transport of molecules to specific compartments of the cell through Brownian motion alone.

Also, self-assembly processes can produce structures that are non-spherical. Just look up DNA nanotechnology, which can create nearly any arbitrary 2D or 3D shape.
 
  • #84
Pythagorean said:
This has more to do with the inadequacies of your analogy (such basic analogies can only be carried so far).
Diderot said:
To what do you think my analogy is referring?
Pythagorean said:
cellular processes, what else?
The Lego analogy was referring to imaginary cell parts without difference in shape and way too many possibilities to connect. The analogy is part of step by step reasoning towards the necessity of highly specified parts (very much unlike Lego parts).
Diderot said:
If the different bits have the possibility to form all sorts of chemical bonds the only result can be chaos.
Random movement of Lego parts cannot explain a complex Lego car.
So the different bits must all be highly specified and have just one possibility to fall into place.
There is no point in telling me that the analogy is inadequate in regard to real cellular processes, because that is exactly what I’m trying to point out.
 
  • #85
Darwin123 said:
The motion of the molecules is not directed by any intelligence, so far as we can tell. So far, the molecules seem to be governed by the same rules of physics as is the case in nonliving organisms.
ScienceDaily (Sep. 16, 2012) — Johns Hopkins scientists report what is believed to be the first evidence that complex, reversible behavioral patterns in bees -- and presumably other animals -- are linked to reversible chemical tags on genes. http://www.sciencedaily.com/releases/2012/09/120916160845.htm
> The question is: 'who is controlling the epigenetic switchboard’? <
 
  • #86
Darwin123 said:
The motion of the molecules is not directed by any intelligence, so far as we can tell. So far, the molecules seem to be governed by the same rules of physics as is the case in nonliving organisms.

Diderot said:
ScienceDaily (Sep. 16, 2012) — Johns Hopkins scientists report what is believed to be the first evidence that complex, reversible behavioral patterns in bees -- and presumably other animals -- are linked to reversible chemical tags on genes. http://www.sciencedaily.com/releases/2012/09/120916160845.htm
> The question is: 'who is controlling the epigenetic switchboard’? <

Intelligence, to the extent that it is a useful concept(s) in science, never means that the laws of physics are violated. As an example, this link from the evolution faq uses the term "intelligence" in a way consistent with the underlying laws of "physics" (in that artificial world). http://boxcar2d.com/index.html

I don't know about the specific case in the Feinberg paper, but there is a notion of "swarm intelligence" applicable in some circumstances to bees. http://www.scholarpedia.org/article/Swarm_intelligence

Here is a free article that discusses some molecular details that may be relevant.
http://www.ncbi.nlm.nih.gov/pubmed/15572455
"Here, we report on the identification of a substance produced by adult forager honey bees, ethyl oleate, that acts as a chemical inhibitory factor to delay age at onset of foraging. Ethyl oleate is synthesized de novo and is present in highest concentrations in the bee's crop. These results suggest that worker behavioral maturation is modulated via trophallaxis, a form of food exchange that also serves as a prominent communication channel in insect societies. Our findings provide critical validation for a model of self-organization explaining how bees are able to respond to fragmentary information with actions that are appropriate to the state of the whole colony."
 
Last edited:
  • #87
Diderot said:
The Lego analogy was referring to imaginary cell parts without difference in shape and way too many possibilities to connect. The analogy is part of step by step reasoning towards the necessity of highly specified parts (very much unlike Lego parts).

There is no point in telling me that the analogy is inadequate in regard to real cellular processes, because that is exactly what I’m trying to point out.
And he is pointing out that it is your analogy, having nothing to do with any response others have made to your OP.
Leggo blocks are interesting in that they have been designed to have multiple connection points so that there is no one stable configuration to them. Oddly, this is the opposite of what you are saying. The shapes were carefully designed so that one can make more than one shape. In this case, the corporate chaos in their configuration is the result of design. Leggo's were designed to be random.
Not much different from the computer simulations that impressed you as being random. You did not see pictures of actual molecules forming structures with random motions. These were make believe molecules that were following random paths. The thing is that there could not be any mystical purpose to their motion because these cartoon molecules were programmed not to have any order in their motion.
You initially said that there had to be some order in the motion of the molecules that was the result of some programming or purpose. However, the motion that you saw had actually been programmed not to show any order. Random number generators were used, but the final results are independent of the random number generator chosen. There was no specific random number generator necessary to make the order emerge.
The order that you saw emerge from the cartoon molecules was not due to any organized motion. It came from their initial shapes. I conjecture that you are now going to claim that the shapes had to be programmed according to a certain order. However, that is an issue separate from the initial one of this thread. However, I did try to address that second issue already by referring to a study by Lenski and Blount.
The specific shapes are also due to another type of random variation in the heredity of the organism. Physically, the variation in heredity is random. Scientists have studied the physical processes of inherited variations such as mutation. Again, the direction of inherited variation is for the most part random. They arise through the random motion of molecules, that were already discussed. There is no programming in mutation. So how come the results of many accumulated variations show order? For instance, why do the molecules and processes show shapes far more specific than any Leggo block?
The shapes are determined by a highly unrandom process called natural selection. It is natural selection that makes a generalized shape into a very specific one.
I posted a link about an article by Lenski and Blount. This article showed how random mutations accumulated into very specific chains of chemical reactions. The shapes of some of the molecules changed to make certain chemical reactions more probable and other chemical reactions less probable.
The experiment was very tightly controlled so that each mutation could be tracked back to the original ancestor to whom that mutation occurred. For instance, the bacteria in their experiment were castrated! The cells were mutilated so that they couldn't perform any process similar to sexual reproduction. All these bacteria could do is split. They had to reproduce asexually.
Note that this would have seriously restricted the amount of variation that was possible. Castration should have prevented the bacteria from reaching their full evolutionary potential. The changes observed in this experiment were less than what would have been seen in "wild type" bacteria.
What were seen were huge changes in the chemistry of this bacteria. The castrated bacteria, among other things, evolved to consume citrate in an oxygen atmosphere.
There would probably have been even more amazing changes for a viral bacteria. More sex, more recombination, more inherited variation, and more evolution. So why were the bacteria castrated? To prove something that you are trying hard not to believe.
By tracking each mutation back to the source, Lenski and Blount proved that the mutations were random. No mutation occurred that was so complex it required a programmer to design. These were all "small" mutations. No miracle occurred in anyone generation. They could prove it because they could track the changes.
So here is an example where natural selection, acting on "random mutations", resulted in an "improbable" change. The individual changes were random. However, the accumulated change was not random.
One other thing that may help you understand is the "organized" shape of a snowflake.
Usually we see snowflakes that are clumped together. So few people, at least the urban ones, have seen snowflakes just after they were formed before collision. However, I have been in the country in areas where the snowflakes fall without interference. They are intricate six-fold shapes with amazing order to them.
A few snowflakes are identical. Maybe as many as two snowflakes in a thousand are identical. However, this is a small fraction. The vast majority of snowflakes are not alike. They have amazing variety, yet each type of snowflake shows unmistakable order. Here is something you should consider.
The shape of a snowflake has nothing to do with programming either. A snowflake forms by diffusion. The water molecules in vapor are moving randomly. The water molecules, although simple, have specific shapes. However, each water molecule has a trajectory and an orientation that is random.
The order comes from another type of natural selection. The sticking probability of a snowflake is biased by heat exchange with the atmosphere. The water molecules tend to stick at points on the flake, not flat areas. So a region with lots of points gets more water vapor to make even more points. In other words, the points reproduce with survival of the fittest.
The variation in snowflakes is caused by random variation modulated by a selection process. It isn't selection in the sense of an organism. The selection does not have purpose as animals understand it. However, it is selection. The selection shapes the random process into an order pattern.
Diffusion does result in order. Small variations can accumulate with selection into an ordered pattern. That is self assembly.
 
  • #88
Diderot said:
ScienceDaily (Sep. 16, 2012) — Johns Hopkins scientists report what is believed to be the first evidence that complex, reversible behavioral patterns in bees -- and presumably other animals -- are linked to reversible chemical tags on genes. http://www.sciencedaily.com/releases/2012/09/120916160845.htm
> The question is: 'who is controlling the epigenetic switchboard’? <
I can do one better. I saw a demonstration just yesterday of plastic pieces, not directly controlled by anything, self assemble into a sphere. Here are links to similar demonstrations. You can watch the video and tell us who is controlling the switchboard of these plastic pieces.
The links have a video showing the self assembly of a model of the polio virus. Olson used a computer to carve models of pieces of the polio virus capsid. Magnets were placed at the edges of the pieces. The pieces fit together to form a spherical shaped body, which is a model of the entire polio virus.
I just attended a seminar by Olson where he demonstrated this “self assembly” among other things. After I the seminar, he let me shake the container myself. The sphere rearranged several times when it was “softly” shaken. Note that one can see many failed “attempts” by the pieces to rearrange themselves. However, these intermediate forms fall apart. The final result is one of two stable forms for the polio capsid.
Olson places the sphere in a sealed container. When he shakes vigorously, the sphere breaks up into separate pieces. When he shakes gently, the pieces assemble into the sphere.
One caveat. Without a core, there are two stable forms of the capsid. One stable form has a trapped piece inside the nearly assembled capsid. There is a hole in the capsid. Olson assured me that could be prevented by placing a model of the RNA core in the container. That is closer to the situation in a real cell, where the stable form with the hole doesn’t occur. However, he didn’t include the core in the container that I shook. the version of the simulation that I took part in had two outcomes. A capsid with a hole in it occurred about half the trials.
The motion is not “programmed”, beyond the amplitude of the shaking. The vigor of the shaking is analogous to temperature. However, the motion of the pieces is random. This is how the OP originally framed her question. The statement is there had to be some will governing the motion of the pieces. This clearly is not true.
If there is programming involved, then it is in the shapes of the separate pieces. There is no purpose and no will to the individual motions.
He also described experiment where he mixed two types of pieces of opposite chirality. When shaken, the mixture formed two polio virus models of opposite chirality. So the fact there is more than one “stable structure” is irrelevant. The random motion ends up separating the assembled pieces. I didn’t see that demonstration, but I have no difficulty believing it.
He also claims to have done the experiment with an automatic shaker. The pieces still assembled. There was no programming in the shaker. When the shaking was restricted to a range of vigor, the sphere self assembles.

Short link showing just the self assembly of the polio virus model.

”Arthur Olson (www.mgl.scripps.edu ) gives a very engaging demonstration of how molecular recognition and self-assembly can be explored using an innovative, hybrid user interface that combines 3D solid printing…”

Longer video with a more complete lecture. Basically, he is talking about a new type of computer interface which he used in making these pieces of polio virus. However, this discussion may give you a better idea of how biochemists see the universe.
http://vimeo.com/26198903
“Arthur Olson (mgl.scripps.edu) gives a very engaging demonstration of how molecular recognition and self-assembly can be explored using an innovative, hybrid user interface that combines 3D solid printing and his own augmented reality environment. He argues that a synthesis of both abstract & 3D visualization is needed to understand biological processes. He then presents impressive, cutting-edge methods for fast, integrated, and large-scale macromolecular visualization. This talk was presented at VIZBI 2011, an international conference series on visualizing biological data (vizbi.org) funded by NIH & EMBO. This video was filmed and distributed with permission under a creative common license.”
 
Last edited by a moderator:
Back
Top