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How to picture the cell?

 
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Sep22-12, 02:15 PM   #69
 
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How to picture the cell?


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.
 
Sep22-12, 06:40 PM   #70
 
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Quote by Ygggdrasil View Post
"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?
 
Sep22-12, 09:50 PM   #71
 
Quote by atyy View Post
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.
 
Sep22-12, 10:54 PM   #72
 
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Quote by atyy View Post
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.
 
Sep28-12, 08:16 AM   #73
 
Quote by Ryan_m_b View Post
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.
 
Sep28-12, 08:19 AM   #74
 
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Quote by Darwin123 View Post
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.
 
Sep29-12, 12:55 PM   #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.
 
Sep29-12, 01:49 PM   #76
 
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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/public...art1_QRB02.pdf
http://www.haverford.edu/biology/Cou...io303_dill.pdf
http://people.virginia.edu/~dta4n/bi...dingIandII.pdf
 
Sep29-12, 03:04 PM   #77
 
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Quote by Diderot
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:

Quote by Choi, et al
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/
 
Sep29-12, 08:14 PM   #78
 
Quote by Pythagorean View Post
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?
 
Sep29-12, 10:11 PM   #79
 
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Quote by Diderot View Post
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.
Quote by Pythagorean View Post
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 ?
 
Sep29-12, 10:39 PM   #80
 
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Quote by Diderot View Post
To what do you think my analogy is referring?
cellular processes, what else?

Quote by atyy
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.
 
Sep29-12, 10:43 PM   #81
 
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Quote by Pythagorean View Post
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_priz...on-speech.html
 
Sep29-12, 10:52 PM   #82
 
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Regardless, there's no "program of the cell".
 
Sep29-12, 11:29 PM   #83
 
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Quote by Diderot View Post
- 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.
 
Sep30-12, 05:54 AM   #84
 
Quote by Pythagorean View Post
This has more to do with the inadequacies of your analogy (such basic analogies can only be carried so far).
Quote by Diderot View Post
To what do you think my analogy is referring?
Quote by Pythagorean View Post
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).
Quote by Diderot View Post
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.
 
Sep30-12, 06:26 AM   #85
 
Quote by Darwin123 View Post
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...0916160845.htm
> The question is: 'who is controlling the epigenetic switchboard’? <
 
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