Can self-assembling molecules show us how cells function?

[Diderot]

I'm a biology dilettante who is trying to get a correct picture of the cell. From this web page http://www.arcfn.com/2011/07/cells-are-very-fast-and-crowded-places.html one gets a very chaotic impression. Small molecules are racing around with 250 miles per hour.
Ken Shirrif: "In addition, a typical protein is tumbling around, a million times per second. Imagine proteins crammed together, each rotating at 60 million RPM, with molecules slamming into them billions of times a second. This is what's going on inside a cell."
I was wondering if this is a commonly held view here or that someone is willing to dispute this.

 

[Simon Bridge]

Welcome to PF;
That would appear to be pretty standard - to put it in perspective, though, geologists commonly talk about continents wizzing around and crashing into each other. Your understanding should be tempered with the scale of these events. The constituents of the cell are very small against everyday scales so the chaotic jumble is normal.

The cell is certainly not the structured and ordered factory/machine that used to be portrayed when I was a kid.

 

[Pythagorean]

Here's what it might look like inside a insulin-producing pancreas cell if we color code it:

http://learn.genetics.utah.edu/content/begin/cells/membranes/images/tomography.jpg

from:
http://learn.genetics.utah.edu/content/begin/cells/membranes/

Of course, understanding the cartoon picture is the first step to understanding the major functioning parts:

http://web.jjay.cuny.edu/~acarpi/NSC/images/cell.gif

 

[mishrashubham]

I'm a biology dilettante who is trying to get a correct picture of the cell. From this web page http://www.arcfn.com/2011/07/cells-are-very-fast-and-crowded-places.html one gets a very chaotic impression. Small molecules are racing around with 250 miles per hour.
Ken Shirrif: "In addition, a typical protein is tumbling around, a million times per second. Imagine proteins crammed together, each rotating at 60 million RPM, with molecules slamming into them billions of times a second. This is what's going on inside a cell."
I was wondering if this is a commonly held view here or that someone is willing to dispute this.

That isn't really strange at the molecular scale. It's not just the cell, any fluid mixture is like that. All the molecules in a glass of water are whizzing around at those very 'phenomenal' speeds. So are the air molecules around you. The only molecular systems where you could say that molecules aren't moving that much would be perfect crystals at nearly absolute zero temperatures.

 

[Ryan_m_b]

The link you posted had a very good video from Harvard, here is it in fullThe usual way that cell biology is taught is to work up in detail and complexity which may explain your surprise. First very simple fried egg-like pictures are shown to young kids at school.

Older students then use more detailed diagrams that show organelles

And beyond that more detailed diagrams of metabolic pathways and organelle structures are used. This is just one simple summary of one small pathway;

Cells are very complicated organisms with tens of thousands of different molecules interacting in metabolic webs all the time. This is what allows them to engage in all the complex behaviours that they need to in order to react to environmental conditions and survive (as well as cooperate).

 

[Diderot]

Thank you all for answering my question. Thanks to you I understand that these speeds are 'perfectly normal' at the molecular scale.
Now 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. So there has to be some sort of guidance for all those parts?

 

[Ryan_m_b]

Thank you all for answering my question. Thanks to you I understand that these speeds are 'perfectly normal' at the molecular scale.
Now 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. So there has to be some sort of guidance for all those parts?

It's not really debatable, it's well studied. I'd advise you to try not to think in analogies to human technology. I know it's hard not to but honestly it will mislead you because the similarities are few. Simply put all molecules act in accordance to thermodynamics and their chemical properties. Biology is fundamentally a collection of continuous chemical reactions that give rise to homeostatic phenomena. Proteins for example will fold into the most energetically favourable configuration through molecular interaction with the environment and themselves (e.g. sulpher bonds between amino acids).



The scope of behaviour available is due to the incredible complexity and redundancy born from billions of years of evolutionary history.

 

[Andy Resnick]

Thank you all for answering my question. Thanks to you I understand that these speeds are 'perfectly normal' at the molecular scale.
Now 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. So there has to be some sort of guidance for all those parts?

Trafficking of proteins is an active area of research- some proteins, after being expressed, are then modified (acetylated, methylated, etc). Others are sent to specific locations in the cell (e.g. ciliary membrane), and others (cytoskeletal proteins) undergo polymerization/depolymerization cycles and are stored in 'pools'. "bad"- misfolded or damaged proteins- are sent to special organelles to be recycled. Proteins are inserted and removed from membranes, and as Ryan_m_b posted, there's coordinated motion of multiple proteins as well (signalling pathways). Much research is oriented towards understanding and controlling these dynamics.

I wouldn't say there's 'guidance', tho. For example, simple hydrophobic/hydrophilic considerations allow for a wide range of organized stable structures.

 

[Diderot]

(...) Others are sent to specific locations in the cell (...)

Do you mean by ‘are sent to’ anything other than that proteins happen to arrive at the right location by chance; because by their speed and rotation they cover so much ground?
For instance: the correct protein 'happen' to slam into a receptor of the correct organelle?

 

[Ryan_m_b]

Do you mean by ‘are sent to’ anything other than that proteins happen to arrive at the right location by chance; because by their speed and rotation they cover so much ground?
For instance: the correct protein 'happen' to slam into a receptor of the correct organelle?

In some cases it is due to diffusion in others due to transport via the cytoskeleton (as shown in the "inner life of the cell" video embedded about).

 

[Simon Bridge]

I'd add here:
Another way of looking at it is to consider that you are constantly moving, often at whole meters per second, and yet you can still have meaningful interactions with other humans also in constant motion ... you manage to get into the right position to do so. It does not always work - see how many people you have to ask out before you get a date for instance.

The reason you can do this is that the interactions are on a time-scale that is small enough that the motions of you and others do not matter so much. (They still hinder you - just not fatally.) On top of this, you are not entirely passive in the process - you don't just, for instance, just ask everyone you see for a date: you try to ask people who you are attracted to and who appear attracted to you.

It is the same in the cell - though 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.

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.

-----------------
Aside: scientists, particularly evolutionists, often talk about things happening by "chance". It is easy to confuse this with ideas about "randomness". This is not the case - the processes in the cell are not random. Bits don't "happen" to arrive in "just the right place" to do something. What they mean by "chance" is that the exact motion at any time cannot be anticipated.

To get a picture of the difference - you may drive home after work and end up stuck behind a bus in slow traffic. That is a chance event in that you could not have anticipated the bus being right there. Yet this was not random - you left work at the time you did for a reason, the bus follows a route and tries to follow a timetable. Each of you got various delays and breaks in your travel which ended up with you stuck behind the bus.

Now with all the traffic and the amount of driving you do in your lifetime - it is actually inevitable that you will get stuck behind a bus sometime (unless you don't drive...). This is certain, even though it is entirely a chance occurence.

 

[Diderot]

In some cases it is due to diffusion in others due to transport via the cytoskeleton (as shown in the "inner life of the cell" video embedded about).

Which mechanism is dominant in the cell 'diffusion' or 'transport'?

It does not always work - see how many people you have to ask out before you get a date for instance.

I'm not willing to discuss this. But seriously, your analogies are very helpful. Thank you.

 

[atyy]

"A small molecule such as glucose is cruising around a cell at about 250 miles per hour"
250 miles/hour = (250*1609 meters)/(60 *60 seconds) = 100 meters/second.

"A small molecule can get from one side of a cell to the other in 1/5 of a second."
If a cell is 0.000100 meters in across, then to get from one side to the other in 1/5 of a second, the speed is 0.00002 meters/second.

Is the speed of 250 miles/hour always in a particular direction? If it is not, the net speed along a particular path over larger time scales might be slower.

 

[Darwin123]

Here's what it might look like inside a insulin-producing pancreas cell if we color code it:

http://learn.genetics.utah.edu/content/begin/cells/membranes/images/tomography.jpg

from:
http://learn.genetics.utah.edu/content/begin/cells/membranes/

Of course, understanding the cartoon picture is the first step to understanding the major functioning parts:

http://web.jjay.cuny.edu/~acarpi/NSC/images/cell.gif

You should have pointed out that the picture that you posted is of a eukaryote cell, not a prokaryote cell. Prokaryotes don't have a nucleus or cytoplasm. Furthermore, prokaryotes don't have the cytoskeleton, the protein network that fills up the cytoplasm of eukaryotes.
Prokaryotes include bacteria and other cells without nuclei. Eukaryotes include protozoa, fungi, plants and animals.
The earliest fossils appear to be from prokaryotes, not eukaryotes. So it is a little misleading to refer to the eukaryote cell as "the first step". There are still more prokaryote cells on Earth than eukaryotes.
Maybe the "first step" should be in understanding the prokaryote cell. A eukaryote cell can be thought of as a "house" for a few prokaryote cells (i.e., nucleus, mitochondria, chloroplasts).

 

[Andy Resnick]

Do you mean by ‘are sent to’ anything other than that proteins happen to arrive at the right location by chance; because by their speed and rotation they cover so much ground?
For instance: the correct protein 'happen' to slam into a receptor of the correct organelle?

I mean that there is both directed transport along cytoskeletal elements such as tubulin and actin in addition to diffusive transport.

Consider a neuron- a long one such as in your arm or leg. If I scaled the axon diameter to 6 feet, the length would be about 200 miles. Diffusive transport is not sufficient to get enough 'stuff' down the pipe.

 

[Darwin123]

I mean that there is both directed transport along cytoskeletal elements such as tubulin and actin in addition to diffusive transport.

Prokaryotes (e.g., bacteria) don't have a cytoskeleton. Therefore, they don't have cytoskeletal elements.
There are components of bacterial cells that may have these elements. Examples would be the cilia and pillai of some Gram-negative bacteria. However, these do no serve the same purpose as the cytoskeleton in eukaryotes.
Bacteria have a lot of enzymes attached directly to their membranes. Thus, the reactions are mediated by the right molecule hitting the right enzyme in the right position.
The prokaryote cell fits the description of the OP very well. The eukaryote cell fits the description a little less well because of the cytoskeleton. Eukaryotes have evolved a cytoskeleton that channels some of the molecular motions, selecting those that are more productive. However, the prokaryote ancestors of eukaryotes probably didin't have a cytoskeleton.
Apparently, a cell doesn't need a cytoskeleton to survive. A cell needs a cytoskeleton to compete with other cells. The first eukaryote found the extra efficiency provided by the cytoskeleton useful in competing with prokaryotes. However, the full machinery of the cytoskeleton probably didn't develop in one step.
So most of the collisions are nonproductive. The probability per collision with the cell membrane that the molecule hits the right enzyme in the right state is small. However, millions of such collisions occur every second. So the probability that a right collisions occurs after a few seconds is very high.

Consider a neuron- a long one such as in your arm or leg. If I scaled the axon diameter to 6 feet, the length would be about 200 miles. Diffusive transport is not sufficient to get enough 'stuff' down the pipe.

However, diffusive transport gets "stuff" across the pipe. Material 'stuff' is not transmitted down the pipe. Electrochemical signals are sent down the pipe.
Diffusive transport is characteristic of Markovian motion. Many of the calculations of probability that evolution skeptics give are based on Markovian motion. However, the motion of molecules in a cell are not completely Markovian. The concentration of molecules in a cell membrane are too high for Markovian motion.

 

[Darwin123]

Which mechanism is dominant in the cell 'diffusion' or 'transport'?

Physicists and biologists think of diffusion as one specific type of diffusion. Transport is any process that gets a scalar from one location to the other. Two types of transport studied by physicists and biologists are diffusion and advection.
Diffusion is the transport that is characterized by "random" motions of the molecules. Advection is the transport that is characterized by "coherent" motion of the molecules.
On large distance scales, advection is usually greater than diffusion. On distance scales comparable to the diameter of a prokaryote cell, diffusion is usually greater than advection.
Eukaryote cells are broken up into compartments called organelles. Each organelle has a size on the order of a prokaryote cell. Therefore, diffusion dominates within an organelle. However, the cytoskeleton provides a type of advection between organelles. Advection is at least as important as diffusion between organelles.
I think the OP was asking about chemical reactions that occur inside prokaryotes or inside organelles. On this distance scale, collisions are truly random. However, the probability per collision of a useful chemical reaction is relatively high. There are millions of collisions per second, so a useful reaction are quite probably in one second.
The correct answer to the OP's question may be this. The description of "random collisions" at a "rapid rate" is probably valid inside a prokaryote cell. However, eukaryote cells have a higher level of complexity. The description of "random collisions" at a "rapid rate" is probably valid inside individual organelles of the eukaryote cell, but not in the cytoplasm between organelles. Between organelles, one has to take into account the cytoskeleton.
One way to visualize this is to think of some of the organelles as being prokaryotes. Some prokaryotes evolved to live together as a eukaryote cell. The cytoskeleton is a "telephone network" to aid communication between prokaryote cells. A eukaryote cell is basically a colony of prokaryote cells.

 

[Pythagorean]

particularly, the type of diffusion being considered recently is anamolous diffusion (as opposed to the classical diffusion usually considered). The basic idea is analogous to the perfumed room:

Using passive/classical diffusion, in a "standard" sized classroom, if you squirted a little perfume in one corner, it would take about ten minutes for the smell to reach the opposite side of the room via passive diffusion.

In the real world, we observe that it actually takes much less time because of all the convective currents in the room that actively transport the perfume particles much faster than passive diffusion would. So we expect in a cell, where there's a lot of action (interaction and reaction) going on that transport woud actually be much more anamolous than we have classically considered.

Mathematically, this is represented by fractal derivatives. Classical diffusion utilizes the integer derivative (n=1) but anamolous diffusion comes in two varieties where n can now be a decimal (the significance of this is that coupling is no longer nearest-neighbor, but global). If n>1, we have superdiffusion, if n<1, we have subdiffusion.

Much evidence lately has shown that diffusion processes in the cell could be super-diffusive. But some computer simulations show that subdiffusion might be better for target delivery:

http://biocomplexity.indiana.edu/jglazier/docs/papers/54_Anomalous_Diffusion.pdf
http://md1.csa.com/partners/viewrecord.php?requester=gs&collection=TRD&recid=14419441SO

 

[Diderot]

So small molecules are moving and rotating really fast and larger molecules relatively slower. But how about the nuclear membrane, the cytoskeleton and the cell membrane? Should one consider these elements as static?
And how about the cell membrane of prokaryotes?

 

[Darwin123]

particularly, the type of diffusion being considered recently is anamolous diffusion (as opposed to the classical diffusion usually considered). The basic idea is analogous to the perfumed room:

Using passive/classical diffusion, in a "standard" sized classroom, if you squirted a little perfume in one corner, it would take about ten minutes for the smell to reach the opposite side of the room via passive diffusion.

In the real world, we observe that it actually takes much less time because of all the convective currents in the room that actively transport the perfume particles much faster than passive diffusion would. So we expect in a cell, where there's a lot of action (interaction and reaction) going on that transport woud actually be much more anamolous than we have classically considered.

Mathematically, this is represented by fractal derivatives. Classical diffusion utilizes the integer derivative (n=1) but anamolous diffusion comes in two varieties where n can now be a decimal (the significance of this is that coupling is no longer nearest-neighbor, but global). If n>1, we have superdiffusion, if n<1, we have subdiffusion.

Much evidence lately has shown that diffusion processes in the cell could be super-diffusive. But some computer simulations show that subdiffusion might be better for target delivery:

http://biocomplexity.indiana.edu/jglazier/docs/papers/54_Anomalous_Diffusion.pdf
http://md1.csa.com/partners/viewrecord.php?requester=gs&collection=TRD&recid=14419441SO

I can add another citation, although I can't provide an active link.
There is an article in the most recent Physics Today that discusses many of these topics. The article is:
"Strange Kinetics of Single molecules in Living Cells" by Eli Barai, Yuval Garini and Ralf Meltzer. Physics Today Volume 65 Number 8, page 29-35 (August 2012).
It points out that most of the diffusion going on in the cell is anomalous diffusion. The diffusion is not governed by standard Markovian walks.
For instance, ergodicity is not always satisfied by the motions of a molecule in a single cell. Furthermore, diffusion is not always stationary. The conditions in the cell change so rapidly that the environment at the beginning of a molecules trajectory is not the same as the environment later in the trajectory.
So there is a separate process, called "subdiffusion", riding on the "normal" diffusion of a molecule. Thus, time averaged observables are not always reproducible. Since time averaging of handling most "random" variables, other mathematical approaches have to be developed to analyze the data.
The real question is whether this addresses the questions of the OP. If he asks whether the molecules are really moving randomly, then he has to tell us what he means by "random". Maybe by "random" is talking only about observables that are ergodic. In other words, he will only accept as random situations where the ensemble average equals the time average. Then in all probability the motion of a single molecule in the cell is not always ergodic. By his definition, it is not random.
The motion of big molecules in the cell are often anomalous, meaning that it doesn't precisely follow the rules of Brownian motion. The probabilities are weighted in a certain way that isn't exactly the same as would occur if the molecules moved like Einstein predicted for Brownian particles.
My suspicion is that he and the person he talked to are thinking about a more teological definition of random. 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.
The statistics may be a skewed in the sense that they are not Gaussian distributed. The Bell shaped curve doesn't seem to govern the probabilities of the important events. However, there is nothing unnatural in this. Gaussian statistics are not as universal as many statisticians think. In the most general sense, the statistics of the molecules in a cell are random and fast. There are millions of collisions of a molecule with the cell wall per second, and there is no fixed path that governs the trajectory of the motion.
If the OP wants a more specific answer, then he should provide a more specific definition of "random" as he understands it. The word "random" is used in many different ways. There are many random distributions that are different.
My hypothesis is that his use of the word random is close to the definition of ergodic. He may be assuming that the motion of the large molecule in a cell eventually reaches every possible position with equal frequency given sufficient time. If that is what he means, then I would say no. The motion of a large molecule in a cell is not completely ergodic.

 

[Mike H]

The notion that bacteria don't have a cytoskeleton seems less likely as research progresses. See, for example, the work done by http://www.molbio1.princeton.edu/labs/gitai/ at Princeton, among others. Both actin and tubulin homologs have been found in bacteria. The references section at this Wiki article on the prokaryotic cytoskeleton is probably a good place to start if interested.

So small molecules are moving and rotating really fast and larger molecules relatively slower. But how about the nuclear membrane, the cytoskeleton and the cell membrane? Should one consider these elements as static?
And how about the cell membrane of prokaryotes?

Depends on what you define as static. Does, for example, lateral diffusion of lipids in a membrane count? Or does the membrane as a whole need to deform? What about a protein being transported along a polymerizing actin filament in the same direction of its formation - it's not influenced by the filament forming in front of it nor by the filament coming apart behind it. Look up "treadmilling," which is observed in actin filaments and microtubules.

 

[Darwin123]

Do you mean by ‘are sent to’ anything other than that proteins happen to arrive at the right location by chance; because by their speed and rotation they cover so much ground?
For instance: the correct protein 'happen' to slam into a receptor of the correct organelle?

Eventually. However, your picture is wrong. You are looking only at one outcome that is very rare compared to the other outcomes.
If a protein slams into the "wrong" receptor, then nothing is going to happen. In fact, that is the majority of collisions. In the majority of collisions, the "wrong" collision happens. However, the wrong collision does not have any effect.
Yes, the molecules cover a lot of ground. However, the specificity is usually geometric. The enzyme molecule is shaped so that it will react only with a certain protein molecule. There is a selection process.
Furthermore, all the molecules are moving including in the cell membranes. I am not sure what you mean by the cell membrane being thought of as static. There are enzyme molecules in the cell membrane changing shape.
The general boundaries of the cell membrane are maintained by simple adhesion forces. The cell membrane, aside from the enzyme molecules, is as stable as the micelle membranes in a water-soap-oil suspension.
I am not sure what you are trying to get at when you talk about a static cell membrane. The motion of biomolecules, so far as has been studied, seem to satisfy the same laws of physical chemistry as any other molecule. I am not sure what you mean by "directed". There are no static molecules at temperatures where water is a liquid.
Maybe by directed you mean that the probabilities are "weighted" in the right direction. Or maybe you think a misstep is somehow "punished". Well, this isn't true. The molecules hit plenty of the wrong receptors before they get to the right receptors. The "wrong" choices are selected out by being ignored. There is no "direction" determined by a cytoskeleton in a prokaryote cell.
Prokaryotes do not have a cytoskeleton. Prokaryote cells are much simpler than eukaryote cells. They don't have all the widgets of eukaryote cells. I agree that they are relatively complicated compared to nonliving entities. However, the first living cell was hypothetically prokaryote, not a eukaryote.
I hypothesize that we are seeing a truncated version of the "irreducibly complex" argument. The implicit argument seems to be that since the probabilities of collision in a eukaryote cell seem weighted, and since the weighting is needed for the cell to survive, there has to be a "direction" that determines the weighting. If you are presenting question based on "irreducibly complex" reaction, then the drawings of a eukaryote cell (e.g., presented by Behe) are misleading. What Behe should have started with is a prokaryote cell.
Prokaryote seem to survive quite well. In fact, the majority of cells on Earth are prokaryotes. Many of the processes that seem so efficient in eukaryotes are not so efficient in prokaryotes. The inefficiency of some of their chemical processes have not diminished their success in terms of numbers. The processes that we see in eukaryote cells do not seem to be "irreducibly complex" when we consider prokaryote cells. Most of the processes in eukaryote respiration, digestion, and reproduction have simpler analogs among the prokaryotes. So if you want to establish that a process is "irreducibly complex" in eukaryotes, you have to first eliminate the possibility that a simpler homolog isn't pro
The fossil evidence seems to indicate that prokaryote came into existence "rapidly" (less than 200 million years) after the Earth solidified. Then, some of them evolved into more complicated forms over time.
If you want to discuss abiogenesis, then you should start with the prokaryote cell. You have to discuss the possibility of a very small prokaryote cell developing, with enzymes that are not as specific as they are today. Furthermore, you have to discuss long periods of time with lots of material dispersed throughout the earth.
The complex shape of enzymes, which makes the reactions so specific, are not necessary for the bare survival of a single prokaryote cell. Prokaryote cells are relatively unspecific. They exchange genetic material even with cells of other species of prokaryote, and sometimes with eukaryote cells. So arguments based on the specificity of todays organisms aren't really convincing.

 

[Pythagorean]

So small molecules are moving and rotating really fast and larger molecules relatively slower. But how about the nuclear membrane, the cytoskeleton and the cell membrane? Should one consider these elements as static?
And how about the cell membrane of prokaryotes?

I know that at least in the case of neurons, where they meet at synapses and gap junctions, the contact area determines how information transfer is negotiated, lots of change occurs over night. The simplest explanation is that the "strength" of the connection is regulated by contact area.

When we sleep, a lot of memory consolidation occurs. Experiments on astrocytes have demonstrated that night time cues lead to heavy transcription and trafficking of fabp7 (fatty acid protein binder for the brain) and psd95 (post synaptic density) occurs. So this has implications for membrane transformations in the dendrite spines of neurons on a daily basis.

 

[Andy Resnick]

Prokaryotes (e.g., bacteria) don't have a cytoskeleton. Therefore, they don't have cytoskeletal elements. <snip>

There are significant differences between eukaryotes and prokaryotes, but there are indeed cytoskeletal filaments:

http://en.wikipedia.org/wiki/Prokaryotic_cytoskeleton

And in any case, this does not invalidate the observation that some proteins are located in highly localized portions of the cell: as you mention, the cilium/flagellum is host to a variety of specific proteins found nowhere else. Diffusive transport works in opposition to this observation, thus the correct mechanism is protein sorting and directed transport (even though the details of the mechanism are currently poorly understood).

However, diffusive transport gets "stuff" across the pipe. Material 'stuff' is not transmitted down the pipe. Electrochemical signals are sent down the pipe. <snip>

This is not true- there are no ribosomes at the distal end of an axon (or within the cilium!), so all proteins *must* be trafficked to the site. All the machinery to allow endocytosis/exocytosis, specific ligand receptors, the neurotransmitters themselves, the axon structural components, etc. all must be transported down the pipe (and the return circuit is important as well, for damaged material as well as nuclear signalling pathways).

 

[Pythagorean]

The video picked out of the OPs link by Ryan actually shows the transport protein, kinesin (or it may have been dynein) dragging cargo across a microtubule. It looks kind of like a giant blob on a leash getting dragged by a little walking protein.

 

[Diderot]

Physicists and biologists think of diffusion as one specific type of diffusion.

I assume you mean 'one specific type of transport'
But you have answered my question very clearly:

On distance scales comparable to the diameter of a prokaryote cell, diffusion is usually greater than advection.

I am not sure what you mean by "directed".

Actually I did not use the term 'directed'. However I did use the term 'guidance' when I introduced the car workshop analogy.
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]

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.

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).

 

[Diderot]

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.

Probably not... unless the program is the laws of physics itself, in which case everything runs under its guidance. (…)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).

I’m starting to understand. There cannot be a ‘program of the cell’, because there is no such a thing as ‘the cell’. There is no ‘whole’ (the cell) which ‘exits’. There are just parts which happen to work together; ontological irrelevant cooperation. Ok, but why stop there? In fact not only is there no cell, there are also no mitochondria, ribosomes, golgi apparatus or amino acids. There are just matter and energy. These are the only wholes that exist, everything else is an illusion.
I’m starting to understand thanks to this consistent line of thought. But wait a minute … there is no such thing as ‘thought’ or ‘understanding’. There cannot be, because there are just matter and energy, which are obviously not interested in illusionary activities like ‘understanding’, ‘overview’ or other mental activities (which of course do not exist). Come to think of it there cannot be even such a thing as ‘I’ …
Reductionism is not a very satisfactory explanation to the human mind indeed, mr. Pythagorean!

 

[Ryan_m_b]

I’m starting to understand. There cannot be a ‘program of the cell’, because there is no such a thing as ‘the cell’. There is no ‘whole’ (the cell) which ‘exits’. There are just parts which happen to work together; ontological irrelevant cooperation. Ok, but why stop there? In fact not only is there no cell, there are also no mitochondria, ribosomes, golgi apparatus or amino acids. There are just matter and energy. These are the only wholes that exist, everything else is an illusion.
I’m starting to understand thanks to this consistent line of thought. But wait a minute … there is no such thing as ‘thought’ or ‘understanding’. There cannot be, because there are just matter and energy, which are obviously not interested in illusionary activities like ‘understanding’, ‘overview’ or other mental activities (which of course do not exist). Come to think of it there cannot be even such a thing as ‘I’ …
Reductionism is not a very satisfactory explanation to the human mind indeed, mr. Pythagorean!

You seem to be diving off of the deep end here but I'll give this thread a chance to continue. When Pythagorean spoke of the program being the laws of physics he meant that there was no top down regulator that viewed and organised all the biochemical pathways in the cell. I don't know why you've run away with that to the point of concluding that nothing exists except as an illusion.

Like with all language we use words to identify objects and concepts from others, these words will rely on a combination of characteristics. Whilst there is always scope for grey areas (i.e. when something has not all the characteristics) that does not mean that we can conclude that what we are identifying does not exist. It could mean that the manner in which we are identifying it is flawed or that we aren't choosing a good system of identification for what we want but that's besides the point.

 

[Evo]

This has strayed WAY off topic. Please return to discussion of the OP.

 

[Diderot]

This has strayed WAY off topic. Please return to discussion of the OP.

My special thanks to Darwin123 for his patience and effort. I fully enjoyed our debate which ended so very abruptly.

 

[Evo]

My special thanks to Darwin123 for his patience and effort. I fully enjoyed our debate which ended so very abruptly.

Please be careful not to derail threads going forward.

 

[Darwin123]

Which mechanism is dominant in the cell 'diffusion' or 'transport'?

Physicists and biologists think of diffusion as one specific type of transport. Transport is any process that gets a scalar from one location to the other. Two types of transport studied by physicists and biologists are diffusion and advection.
Diffusion is the transport that is characterized by "random" motions of the molecules. Advection is the transport that is characterized by "coherent" motion of the molecules.
On large distance scales, advection is usually greater than diffusion. On distance scales comparable to the diameter of a prokaryote cell, diffusion is usually greater than advection.
Eukaryote cells are broken up into compartments called organelles. Each organelle has a size on the order of a prokaryote cell. Therefore, diffusion dominates within an organelle. However, the cytoskeleton provides a type of advection between organelles. Advection is at least as important as diffusion between organelles.
I think the OP was asking about chemical reactions that occur inside prokaryotes or inside organelles. On this distance scale, collisions are truly random. However, the probability per collision of a useful chemical reaction is relatively high. There are millions of collisions per second, so a useful reaction are quite probably in one second.
The correct answer to the OP's question may be this. The description of "random collisions" at a "rapid rate" is probably valid inside a prokaryote cell. However, eukaryote cells have a higher level of complexity. The description of "random collisions" at a "rapid rate" is probably valid inside individual organelles of the eukaryote cell, but not in the cytoplasm between organelles. Between organelles, one has to take into account the cytoskeleton.
One way to visualize this is to think of some of the organelles as being prokaryotes. Some prokaryotes evolved to live together as a eukaryote cell. The cytoskeleton is a "telephone network" to aid communication between prokaryote cells. A eukaryote cell is basically a colony of prokaryote cells.

 

[atyy]

The cytoskeleton is a "telephone network" to aid communication between prokaryote cells.

What are some examples of this?

 

[Pythagorean]

What are some examples of this?

http://www.ncbi.nlm.nih.gov/books/NBK9964/

 

[Diderot]

(...) the components of the cell work together so nicely simply because that combination of matter happened to work out so nicely. (...)

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? The smallest change (mutation) can destroy this balance, and shatter the coincidental cooperation of the parts?
And is it fair to say that this balance is unsupported? 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?

 

[Ryan_m_b]

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? The smallest change (mutation) can destroy this balance, and shatter the coincidental cooperation of the parts?
And is it fair to say that this balance is unsupported? 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?

No, homeostasis takes care of matters like these. Cells can respond to changes in the environment in ways that counter whatever negative condition has arisen. A good example is the hypoxia (low oxygen) response pathway.

In human cells the protein HIF1-a is constantly synthesised but immediately destroyed via an oxygen dependent reaction. In low oxygen this degredation reaction stops "stabilising" HIF1-a. These proteins then migrate into the nucleus to form the HIF1 transcriotion factor which causes the activation of a myriad of genes involved in pathways that will help the cell survive e.g. by upregulating glycolysis and releasing angiogenic factors to bring more oxygen.

 

[Diderot]

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? The smallest change (mutation) can destroy this balance, and shatter the coincidental cooperation of the parts?
And is it fair to say that this balance is unsupported? 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?

No, homeostasis takes care of matters like these. Cells can respond to changes in the environment in ways that counter whatever negative condition has arisen. A good example is the hypoxia (low oxygen) response pathway. (…)

I do not think that this is an answer to my question. The parts of the cell that constitute homeostasis are obviously part of the chemicals that are in a ‘delicate balance’.
So the question ‘is there an unsupported delicate balance between all the chemical reactions in the cell?’ includes the chemicals in the cell that constitute homeostasis.

 

[Ryan_m_b]

I do not think that this is an answer to my question. The parts of the cell that constitute homeostasis are obviously part of the chemicals that are in a ‘delicate balance’.
So the question ‘is there an unsupported delicate balance between all the chemical reactions in the cell?’ includes the chemicals in the cell that constitute homeostasis.

Why isn't it an answer to your question? If something were to damage a cell or require a change in behaviour (including hypothetical spontanous breakdown of a pathway) this itself will cause changes that deal with the issue. Within reason of course, cells aren't immortal. Too much damage at once or over time will ensure that the cell dies no matter what it tries.

 

[Diderot]

Why isn't it an answer to your question? If something were to damage a cell or require a change in behaviour (including hypothetical spontanous breakdown of a pathway) this itself will cause changes that deal with the issue. Within reason of course, cells aren't immortal. Too much damage at once or over time will ensure that the cell dies no matter what it tries.

My question includes the parts which constitute homeostatic activities. If I understand you correctly your answer just seems to shift attention to these parts.
If it is of any help I can rephrase my question like this:
Is it fair to say that there is a very 'delicate balance' between all the chemical reactions of the ‘homeostatic system’ in the cell? There must be an exact amount of everything? The smallest change (mutation) can destroy this balance, and shatter the coincidental cooperation of the parts?
And is it fair to say that this balance is unsupported? Nothing is 'interested' in keeping this delicate balance; not the parts of the ‘homeostatic system’, not the surroundings of the ‘homeostatic system’ and not the ‘homeostatic system’ itself?

 

[Ryan_m_b]

My question includes the parts which constitute homeostatic activities. If I understand you correctly your answer just seems to shift attention to these parts.
If it is of any help I can rephrase my question like this:
Is it fair to say that there is a very 'delicate balance' between all the chemical reactions of the ‘homeostatic system’ in the cell? There must be an exact amount of everything? The smallest change (mutation) can destroy this balance, and shatter the coincidental cooperation of the parts?
And is it fair to say that this balance is unsupported? Nothing is 'interested' in keeping this delicate balance; not the parts of the ‘homeostatic system’, not the surroundings of the ‘homeostatic system’ and not the ‘homeostatic system’ itself?

Yes I understand but this is covered in what I have said previously. To reiterate though:

- No the phrase "delicate balance" is not applicable because in many cases it's not delicate and it isn't a balance.

- No it doesn't require an "exact amount" though many processes require an optimum amount which is regulated, usually by some form of negative feedback.

- That negative feedback is not any kind of top down oversight, it's built into the system (like the oxygen dependent reaction supressing hypoxia response).

- Cells are very redundant, they can take (relatively) a lot of damage before dying and have mechanisms to fix themselves; just look at how robust DNA repair systems are.

- If the damage is such that the cell cannot fix itself then it will die but this is an extensive amount of damage.

Forgive me for being blunt but are you trying to push intelligent design via irreducible complexity here?

 

[Diderot]

Yes I understand but this is covered in what I have said previously. (…)

I do not agree. Thank you for your patience and effort. There is a barrier between us.

Forgive me for being blunt but are you trying to push intelligent design via irreducible complexity here?

No.

 

[Ryan_m_b]

I do not agree. Thank you for your patience and effort. There is a barrier between us.

No worries, feel free to ask further questions. Either I'm missing something or not explaining it well enough and I'm interested in fixing that.

No.

Cool. I had to ask, we frequently get people joining to ask questions like this purely so that they can try to justify their belief (usually by ignoring any post that disagrees with them and taking any post that hints that it does as proof). I'd rather nip it in the bud than waste time.

 

[Diderot]

Cool. I had to ask, we frequently get people joining to ask questions like this purely so that they can try to justify their belief (usually by ignoring any post that disagrees with them and taking any post that hints that it does as proof). I'd rather nip it in the bud than waste time.

I can feel your outrage with these people. Why don’t they embrace the beauty and clarity of reductionism? ‘Homeostasis’ is still no answer to my question though.

 

[Simon Bridge]

What makes you think there is a "delicate balance" at all?

If we can understand the way you use these terms then perhaps the answers can more directly answer the question. As far as I can see, the "homeostasis" answer does answer the question as it is written - especially with the clarification in post #41.

A mechanical example of a delicate balance would be a pin balanced on it's point - it is unstable: the slightest nudge dramatically changes it's state. A pin on it's side is in a stable situation - even quite large nudges still leaves the pin on it's side.

And example of a running mechanical homeostasis would be a steam-engine with a governor - nobody would say the engine is in a "delicate balance" because a small nudge quickly restores it through negative feedback.

Ryan has told you that the processes in a cell are, and the cell itself is, very robust ... it takes quite a big nudge to break them. Therefore, the phrase "delicate balance", as it is usually understood by scientists and engineers, does not apply to the processes in a cell.

 

[Ryan_m_b]

I can feel your outrage with these people. Why don’t they embrace the beauty and clarity of reductionism?

That's not how I feel. In fact I haven't said anything about reductionism, why are you bringing it up and putting these words in my mouth? I feel frustrated when people are willfully ignorant, especially when they waste forum member's time.

‘Homeostasis’ is still no answer to my question though.

I'll try from the beggining. Within a cell there is a myriad of dynamic metabolic pathways active at once (see these images). These pathways interact with each other and the environment and can modify internal processes for different behaviours. When something happens to effect the cell in a negative way (i.e. something disrupts one of these pathways) negtive feedback mechanisms strive to correct this. If the damage is to great or something inhibits the homeostatic mechanisms the cell dies.

 

[Diderot]

If the damage is to great or something inhibits the homeostatic mechanisms the cell dies.

In posting #40 I rephrased my question like this:
Part 1: “Is it fair to say that there is a very 'delicate balance' between all the chemical reactions of the ‘homeostatic system’ in the cell? There must be an exact amount of everything? The smallest change (mutation) can destroy this balance, and shatter the coincidental cooperation of the parts?”
Now you say that if ‘something inhibits the homeostatic mechanisms the cell dies’. So why not answer ‘yes’ to my questions? There doesn’t seem to be a homeostatic system C for homeostatic system B of homeostatic system A, right?

I retract ‘part 2’ of my question in posting #40. This has philosophical implications (reductionism) which I feel no longer free to discuss. Maybe I'm mistaken but I do feel a lack of enthusiasm towards my efforts. Thank you for your time and sharing your thorough knowledge.

 

[Ryan_m_b]

In posting #40 I rephrased my question like this:
Part 1: “Is it fair to say that there is a very 'delicate balance' between all the chemical reactions of the ‘homeostatic system’ in the cell? There must be an exact amount of everything? The smallest change (mutation) can destroy this balance, and shatter the coincidental cooperation of the parts?”
Now you say that if ‘something inhibits the homeostatic mechanisms the cell dies’. So why not answer ‘yes’ to my questions? There doesn’t seem to be a homeostatic system C for homeostatic system B of homeostatic system A, right?

I didn't answer yes because your question was loaded. You're proposing that the system is finely balanced which as as Simon pointed out with his excellent pin analogy doesn't hold. Did you take a look at the images I linked? Metabolic pathways are rarely as simple as A --> B --> C. They are more of a web that generally avoids critical links.

In essence the answer to your question is no. Cells are not finely balanced and are inherently self regulating. To ask whether or not they would die if self regulation was inhibited seems to be a pointless question.

I retract ‘part 2’ of my question in posting #40. This has philosophical implications (reductionism) which I feel no longer free to discuss. Maybe I'm mistaken but I do feel a lack of enthusiasm towards my efforts. Thank you for your time and sharing your thorough knowledge.

What efforts? If you're sensing any negativity it's probably because you keep asking loaded questions, reject the answers you are given without clarifying what you don't understand and post with an undertone that you have an axe to grind wrt "reductionism", I've put that in quotes because you haven't outlined how reductionism comes into your question about cellular biology.

If you want to learn about cellular biology then feel free to continue asking (without the loaded questions), if you want to discuss reductionism then why not start a thread in the philosophy forum?

 

[Simon Bridge]

In posting #40 I rephrased my question like this:
Part 1: “Is it fair to say that there is a very 'delicate balance' between all the chemical reactions of the ‘homeostatic system’ in the cell? There must be an exact amount of everything? The smallest change (mutation) can destroy this balance, and shatter the coincidental cooperation of the parts?”

I don't think it is possible to answer these questions to your satisfaction without first knowing how your use of the words "delicate balance" differ from the usual meanings in engineering and science (particularly biology). If you won't answer questions, we cannot help you.

Now you say that if ‘something inhibits the homeostatic mechanisms the cell dies’. So why not answer ‘yes’ to my questions? There doesn’t seem to be a homeostatic system C for homeostatic system B of homeostatic system A, right?

In the example of a steam engine - I can "inhibit the homeostatic system" by ramming a wrench in the governor. The engine then dies down or explodes. The engine homeostasis is still not a delicate balance in the engineering sense because ramming foreign objects in the works is not a small nudge.

So a cell's homeostasis may be interrupted by injecting a strong acid into it, hitting it with a hammer, being invaded by a virus, stuff like that ... it can even interrupt it's own by apoptosis. Bad damage would trigger apoptosis. But you seem to be asserting that a small change on the scale of cellular processes could catastrophically affect the cell's performance? This is simply not the case and saying "it is" and "I disagree" does not make it so. Perhaps you can provide an example to back up your assertions?

Maybe I'm mistaken but I do feel a lack of enthusiasm towards my efforts. Thank you for your time and sharing your thorough knowledge.

You are mistaken - if there were a "lack of enthusiasm", the thread would be quickly abandoned.

However - if you won't answer direct questions, and reject the answers offered to you, then the enthusiasm will drain away very quickly.

 

[Darwin123]

What are some examples of this?

My speculation, from Margulis, is that many organelles were originally prokaryotes that evolved to be organelles. So I answer your question with two types of links. Articles about communication between organelles in eukaryotic cells, and articles about communication between prokaryotes using filamentary structures.
The first few articles present communication between organelles in the eukaryote cell.

http://www.landesbioscience.com/journals/BioArchitecture/article/20302/
“Crosslinking proteins maintain organelle structure and facilitate their function through the crosslinking of cytoskeletal elements. We recently found an interaction between the giant crosslinking protein dystonin-a2 and the microtubule-associated protein-1B (MAP1B), occurring in the centrosomal region of the cell. In addition, we showed that this interaction is necessary to maintain microtubule acetylation. Loss of dystonin-a2 disrupts MT stability, Golgi organization, and flux through the secretory pathway. This, coupled to our recent finding that dystonin-a2 is critical in maintaining endoplasmic reticulum (ER) structure and function, provides novel insight into the importance of dystonin in maintenance of organelle structure and in facilitating intracellular transport. These results highlight the importance of cytoskeletal dynamics in communicating signals between organelle membranes and the cytoskeleton. Importantly, they demonstrate how defects in cytoskeletal dynamics can translate into a failure of vesicular trafficking associated with neurodegenerative disease.”

http://netresearch.ics.uci.edu/mc/papers/NSTI06.pdf
“A molecular communication system using a network of cytoskeletal filaments.
…
Using molecular communication to control communication between nanomachines is inspired by the observation of biological systems which already commonly communicate through molecules.”

http://www.scielo.br/scielo.php?pid=S0074-02762012000300001&script=sci_arttext
“This review also examines recent data on the presence of nanotubes, which are structures that are well characterised in mammalian cells that allow direct contact and communication between cells.”

http://jcs.biologists.org/content/113/15/2747.full.pdf
“Trafficking and signaling through the cytoskeleton: a specific mechanism
We conclude that diffusion along cytoskeletal tracks is a reliable alternative to other established ways of intracellular trafficking and signaling, and therefore provides an additional level of cell function regulation.”

http://www.scielo.br/scielo.php?pid=S0074-02762012000300001&script=sci_arttext
“Prokaryotic cells: structural organisation of the cytoskeleton and organelles”

The articles below describe specific interactions between prokaryotes using pili, filamentary structures. Thus, filamentary structures are used for communication between free-living prokaryotes.

http://en.wikipedia.org/wiki/Pilus
“A pilus (Latin for 'hair'; plural : pili) is a hairlike appendage found on the surface of many bacteria.[1][2] The terms pilus and fimbria (Latin for 'thread' or 'fiber'; plural: fimbriae) can be used interchangeably, although some researchers reserve the term pilus for the appendage required for bacterial conjugation. All pili are primarily composed of oligomeric pilin proteins.
Conjugative pili allow the transfer of DNA between bacteria, in the process of bacterial conjugation. They are sometimes called "sex pili", in analogy to sexual reproduction, because they allow for the exchange of genes via the formation of "mating pairs". Perhaps the most well-studied is the F pilus of Escherichia coli, encoded by the F plasmid or fertility factor.”

http://faculty.ccbcmd.edu/courses/bio141/lecguide/unit1/prostruct/pili.html
“The short attachment pili or fimbriae are organelles of adhesion allowing bacteria to colonize environmental surfaces or cells and resist flushing. The pilus has a shaft composed of a protein called pilin. At the end of the shaft is the adhesive tip structure having a shape corresponding to that of specific glycoprotein or glycolipid receptors on a host cell (see Fig. 1).
Because both the bacteria and the host cells have a negative charge, pili may enable the bacteria to bind to host cells without initially having to get close enough to be pushed away by electrostatic repulsion. Once attached to the host cell, the pili can depolymerize and enable adhesions in the bacterial cell wall to make more intimate contact.”

I apologize for this fellows compounds sentences. The point is that filamentary structures like pili probably evolved for bacterial cells to bind to other cells.
http://grupos.unican.es/intergenomica/docencia/pdfs/seubert03.pdf
“The identification of transferred substrates would be a major step forward in the molecular understanding of how the B. tribocorum Trw system contributes to pathogenesis.Alternatively, but not mutually exclusively to substrate translocation, the Trw system may have evolved primarily to mediate binding to various host cell structures via surface-exposed pili.”