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The Wave Model for Capping and Cell Motions

Badly Shaved Monkey

Anti-homeopathy illuminati member
Badly Shaved Monkey
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http://freespace.virgin.net/john.hewitt1/pg_ch07.htm

Oh, go on then. Have a thread about it.

Excuse my ignorance, but having read this theory I am at loss to explain exactly what problem it was seeking to address. Perhaps Dr. Hewitt could briefly summarise the idea.

1. What is the question for which an answer was being sought?
2. What is the evidence for the "Wave Model" that distinguishes this from any other model?
3. What relevance has this to cells in multicellular organisms? The reason I ask this is that the model seems to propose that macromolecular cell membrane elements are moved around by physical waves in the cell membrane. Ocean waves cause objects to surf because they interact with the force of gravity. I don't see what force acts as the equivalent to gravity in a 3-dimensional block of cells with surfaces at all orientations.
4. What powers the waves?

Thank you.
 
Not really my department, but I think I can answer a couple of points.

2. I believe the evidence is that cells without cillia, in slime molds in particular, have been seen to have surface waves on them, as described in some of the references. Obviously, these are controversial observations since they appear not to be accepted by most people.

3. The model refers to amoeboid cells, and not eukaryotic cells, so I'm not sure it has any relevance to multi-cellular organisms, not yet at any rate. Also, since the particles are generally ions, electro-magnetic forces would be present. Van der Waals forces would probably be significant enough at these scales anyway.
 
Based on the article, the problem it addresses is how to account -specifically - for the mechanics of movement of particles in cells (a necessary thing since nutrients, waste products and other items must go from place to place within the cell, its' functions to perform). He is pointing out that the advantage in his proposal is that it more fully explains these movements than other models and therefore should be taken seriously and studied further. Though I am undergrad bio only (my background, not right now) his proposal sounds good and seems to be well supported by observation.
 
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As far as what triggers the wave, and assuming I am reading/interpreting correctly: calcium ions (real important in our functions!!). Basically, by selectively releasing/rebinding calcium ions (+) electrical charge on the fluid could repel/attract areas (like hitting the surface of water to create a water wave) to initiate movement (waves).
 
Badly Shaved Monkey said:
Oh, go on then. Have a thread about it.

Excuse my ignorance, but having read this theory I am at loss to explain exactly what problem it was seeking to address. Perhaps Dr. Hewitt could briefly summarise the idea.

1. What is the question for which an answer was being sought?
2. What is the evidence for the "Wave Model" that distinguishes this from any other model?
3. What relevance has this to cells in multicellular organisms? The reason I ask this is that the model seems to propose that macromolecular cell membrane elements are moved around by physical waves in the cell membrane. Ocean waves cause objects to surf because they interact with the force of gravity. I don't see what force acts as the equivalent to gravity in a 3-dimensional block of cells with surfaces at all orientations.
4. What powers the waves?

Thank you.
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Its late right now so I won't yet attempt to answer all your questions. I'll just stick to the first and try to come back in the morning for the rest.

Most readers will know what an amoeba is - a single celled protozoon with a nucleus containing its DNA. It is fairly shapeless and its shape changes as it crawls around on surfaces. Amoebae are eukaryotes – as are all the advanced multicellular animals on earth, such as humans. Many of the cells in a human resemble amoebae in shape and in the way they move, though actual amoebae are usually bigger. Any cell that resembles an amoebae is amoeboid. So, for example, white blood cells are amoeboid but red blood cells are not.

As I said, amoebae move around on surfaces and so do amoeboid cells. The fact that they move is rather important because it is pivotal in how multicellular organisms develop and in many other processes - such as wound healing. However, how they move and how they gather the data needed to guide them is not clear. I have views on the data but here we are just talking about the how.

These cells don't walk, they have no legs, so what is it about the surface that enables them to move? A long thread of experiments in this field focused not on the movement itself but on a closely related pair of phenomena – capping and particle movement. If you drop a small particle onto the surface of a cell, that particle will begin to move backwards, in the opposite direction to that in which the cell is moving. The movement depends on the size of the particle but, generally speaking, not on its chemistry. This sort of thing only happens with motile cells (cells that do move) and this correlation between motility and particle movement is taken to indicate that the mechanism of particle movement is closely linked to that of cell movement – if you understand one, you will understand the other. However, particle movement is much more experimentally accessible than general cell motility so it is studied, effectively, as a proxy to understand the mechanism of motility.

So the proximate question, for which an answer was being sought is, "how and why do particles move on cell surfaces." The more distant question was, "how do cells move?" Motility is a large field and the answer to that question might impact on ideas in perhaps 5-10% of cell biology. Although this may sound like a minor technical question, the answer actually impacts across a wide range of understandings, wider even than is implied by that summary.


So that is my answer to your question number one. It is now 11:30 pm and I think I need to take to bath and bed. I shall return to this tomorrow.
 
Badly Shaved Monkey said:
Thanks for that. I look forward to the next episode.
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Here then is episode 2.

In general then, the prime question is, how and why do cell's move?

Coming on then to your question two, "what is the evidence for the "Wave Model" that distinguishes this from any other model?" I am slightly unclear about what you mean by that question.


You could be asking
2a. What features of the model distinguish the wave model from alternative theories?
2b. What observational evidence supports the wave model over the alternatives?
2c. What observational evidence tends to falsify the alternatives?
In themselves all of those questions are perfectly reasonable but one could give a fairly extended answer to each of them. Such extension is already available on my web site so I won't attempt major detail here.

On that basis my replies to your question 2 are as follows.
2a. The three theories are the "cytoskeletal model," the "flow model" and the "wave model." The cytoskeletal model is currently held to be "correct." The word "cytoskeleton" literally means "cell skeleton" but it is something of a misnomer – these cells have no skeleton but, nonetheless, the cytoskeleton is a real organelle and does determine the cell's shape. The cytoskeleton is actually made from muscle type proteins, so one might think of the cell's shape as being determined by a kind of internal muscle, much as is that of many invertebrates. An actual statement of the cytoskeletal model is difficult to find but the general idea is that, in some way, the cytoskeleton becomes directly linked, through the cell's outer membrane, with external objects which are, in some way, directly transported by cytoskeletal action. A whole variety of actual mechanisms have been proposed for this, many of which actually imply some kind of computational capacity on the part of the cytoskeleton. I have never found any clarity as to which exact mechanism is currently believed and, indeed, it seems to vary from person to person. The clearest evidence against the cytoskeletal is that some membrane components, that clearly do not traverse the membrane, can be aggregated into patches that behave like external particles and move, even though they clearly cannot be in direct contact with an internal cytoskeleton.
In a manner of speaking, I do agree with the cytoskeletal model because the wave model does postulate that the cytoskeleton is producing contractile waves that on the outer membrane. However, that possibility seems to be universally rejected. I have no idea why.

The membrane flow model is quite different. The outer membrane of a cell is a liquid crystal - the membrane is based on lipds which are fluid in the horizontal plane but ordered in the vertical plane. The membrane or lipid flow suggests that the entire outer membrane of the cell is flowing it is internalized at the back, transported through the cell as vesicles and it reformed as membrane at the front. This flow, it is claimed, is sufficient to carry external particles along with it, rather like twigs in a stream.
There is direct, published, observational evidence that the membrane does not flow at the rates required by this model and it is now generally rejected. Nonetheless, some people, notably Bretscher, still profess to believe it.
The mechanism and meaning of this theory seems clear enough. However, to me, it always seemed thermodynamically and evolutionarily unreasonable. It seems t me that membrane flow would require a high energy turnover for the cell and, to my knowledge, such mechanisms of transport do not exist anywhere else in nature.

Those are the two models that received serious attention in the journals - including and influentially in "Nature" under the auspices of John Maddox.

2b. The evidence and arguments favouring the wave model are summarized in chapter 7 of my web site. Aside from direct observations, the most obvious arguments in favour of the wave model are that wave motility recurs throughout the biosphere and does seem to be an energy efficient process. I do not know any serious arguments that falsifies the wave model. However, John Maddox, then editor in Chief of "Nature," did see fit to compare it with the suggestion that the moon is made of green cheese! (Yes, dear reader, he really did.) I presume, therefore, that I am regarded as so ignorant of science that I cannot understand the blindingly obvious, so perhaps some reader here might like to fill me in - metaphorically speaking that is.


2c. The observational evidence tending to falsify the cytoskeletal and membrane flow was given above and is given in more detail on my web site.

I will come back to your question 3 later.
 
John Hewitt said:
Aside from direct observations, the most obvious arguments in favour of the wave model are that wave motility recurs throughout the biosphere and does seem to be an energy efficient process.
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This is where my confusion comes in. Are you saying there are physical oscillatory excursions of the cell membrane? Just like an ocean wave in cross-section?
 
Badly Shaved Monkey said:
This is where my confusion comes in. Are you saying there are physical oscillatory excursions of the cell membrane? Just like an ocean wave in cross-section?
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At this scale, gravity is a negligible force. The interactions that concern us will be mostly chemical and electrical.

I did assume shape variation in my own calculations but I did not think it a necessary assumption, it was just one where I could do some approximate calculations. The two types of wave to consider are spatial waves and waves of electrical polarizaty across the membrane.

However, the point about wave driving as a mechanism of particle movement is that it is fairly independant on the type of wave. The driving force comes from the differences in energy between the particle at different points on the wave. Virtually any mechanism of interaction would produce such differences in energy.

So, the waves as I would envision them could be thought of in two ways. There would be a spatial wave but, in real cells, we also expect to se waves of electrical potential difference, of the order of fraction of a volt, linked to those spatial waves. This would be there for two reasons; first, the mere act of bending a lipid bilayer is expected (as a Bulgarian named Petrov pointed out) to produce a potential difference between the concave and convex surfaces. Also, the contraction of the cytoskeletal elements that are needed to produce waves seems to be under the control of waves of calcium permeability across the membrane. That story is not dissimilar to the nerve impulse story but the waves are slower. Muscle is a multicellular aggregate largely containing cytoskeletal components and we do see waves of calcium permeability and concentration associated with muscle contraction.

If you think about it, a charged particle on the surface of a potential wave will be expected to move with the wave, even if there were no geometric wave associated with it. The size dependancy of particle movement will come from surface area effects. The larger the surface area involved, the larger the energy differences from peak to trough. When the particle gets big enough that the energy diferences start to exceed the thermal randomization energy, then you will start seeing movement.

One cannot do calculations well enought that one could seriously predict the size of particle that would start moving but the observed general pattern is roughly what one would predict from that situation.
 
I don't really see a contradiction between your 'model' and the 'cytoskeletal model'. If as you claim, there is no evidence for a coupling mechanism between the cytoskeleton and the membrane components, would it not be feasible for these electrochemical processes to represent such couplings.

What I don't see in your model is an explanation or refutation of the fact that chemical agents that disrupt the cytokeleton also disrupt patching and capping.
 
Badly Shaved Monkey said:
I don't really see a contradiction between your 'model' and the 'cytoskeletal model'. If as you claim, there is no evidence for a coupling mechanism between the cytoskeleton and the membrane components, would it not be feasible for these electrochemical processes to represent such couplings.

What I don't see in your model is an explanation or refutation of the fact that chemical agents that disrupt the cytokeleton also disrupt patching and capping.
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I do not undertand you problem. One does not refute facts, one attempts to explain them. Nobody disputes that muscle type proteins are involved in cell movement and nobody sensible would be surprised that the agents that disrupt those proteins would also disrup cell movement and asosciated phenomena.

The point at issue is mechanism. Scientific explanations are mechanistic explanations. Merely announcing that "the cytoskeleton causes capping" without giving any mechanistic explanation of what the cytoskeleton does and the mechanism that leads to movement, that is not a mechanistic explanation of anything.

Here is something adapted from my chapter 6, on the cytoskeletal model and why it is so meaningless.

Consider the following theories of capping and particle movement

1. Capping is caused by the cytoskeleton.
2. Capping is caused by the cell.
3. Capping is caused by evolution.
4. Capping is caused by God.

Statements 2 and 3 are, by conventional science, manifestly true, while, depending upon religious standpoints, statement 4 may well be. However, from a scientific perspective, all the statements 2, 3 & 4 have no value. Their very generality means they incorporate all possible experimental outcomes and so cannot predict, or be falsified by, the outcome of any experiment. This was the criterion Popper used to distinguish a scientific from a non-scientific hypothesis. Statements 2, 3 and 4 are not scientific theories with respect to capping.

Statement 1 is hardly more scientific. It has some predictive merit in excluding the idea that other organelles, for example the mitochondria or the nucleus are moving particles and patches. However, nobody has advanced the idea that other organelles are involved and the cytoskeleton is simply an organelle, not a mechanism or a dynamic process. The debate is essentially about how a cell produces force. By far the most natural supposition is that the cytoskeleton, or cytosinew, made from muscle proteins, will be the cell's force generating organelle. This being so, statement 1 above hardly restricts the range of statement 2 at all.

Statement 1 becomes predictively valuable only if it is narrowed down further eg

1A. Capping is caused by the cytoskeleton taking hold of patches and producing forces that reel them in to the rear of the cell. (The original cytoskeletal model).

1B. Capping is caused by the cytoskeleton producing forces that cause the membrane to flow. (The membrane flow model).

1C. Capping is caused by the cytoskeleton continuously assembling at the front of the cell and disassembling at the rear of the cell. (The cytoskeletal flow model).

1D. Capping is caused by the cytoskeleton producing forces that cause travelling wave patterns on the cell surface. (The wave model).

In other words, the issue is not, "does the cell's muscle cause it to move," the issue is, "how does the cell's muscle cause it to move?"
 
John Hewitt said:
In other words, the issue is not, "does the cell's muscle cause it to move," the issue is, "how does the cell's muscle cause it to move?"
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OK.

If it is via waves, what are you saying is the evidence for this. I don't think I could tell from your website what evidence tells us that particles are moved by waves.

Also, to return to the mature of the waves, you say that physical geometric waves may be involved, "There would be a spatial wave", but what entrains anything to 'surf' on that wave? I can't readily see any force other than gravity doing this job. Isn't a spatial wave defined and determined by forward motion and gravity actiing perpendicularly to that motion? This is not, for the moment, considering the possibility of electrical waves, but it is questioning the likelihood of any spatial wave being relevant in a real-world 3-D situation. It's that I can't see how a spatial wave creates a surfing entrainment unless gravity is involved and gravity can't be relevant to the real-world case we are discussing.
 
John Hewitt said:
Its late right now so I won't yet attempt to answer all your questions. I'll just stick to the first and try to come back in the morning for the rest.
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How about these two, which you have still failed to answer in the other thread, despite several reminders:
Mojo said:
Dr. Hewitt, do you consider it acceptable for the manufacturers of homoeopathic "medicines", which you have conceded are worthless, to make therapeutic claims on the packaging of "medicines" sold directly to the general public? Do you think that the government should permit them to make misleading claims?
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Badly Shaved Monkey said:
OK.

If it is via waves, what are you saying is the evidence for this. I don't think I could tell from your website what evidence tells us that particles are moved by waves.

Also, to return to the mature of the waves, you say that physical geometric waves may be involved, "There would be a spatial wave", but what entrains anything to 'surf' on that wave? I can't readily see any force other than gravity doing this job. <snip> It's that I can't see how a spatial wave creates a surfing entrainment unless gravity is involved and gravity can't be relevant to the real-world case we are discussing.
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First, the evidence that waves are involved in particle movement. First, in a couple of systems, particle movement is a physiological requirement, the most notable example being the mucociliary escalator in the lung. In these cases, particle movement is known to be wave driven, albeit that the cells of that tissue is ciliated. Particle movment is often what is called saltatory or stop start. In some instances backward motions are observed, that is the particle moves along, comes to a stop and reverses direction and goes backward briefly before resuming its pirary course. (I leave the interpretation to you.) Sheetz and his coworkers described "dramatic waves" on their fish keratocytes which move "in concert" with the particles. (Though they failed to mention these facts in their "Nature" paper or the obvious interpretation.) Such things are described in more detail in chapter 7.

Second, forget about gravity. This is a matter of dimensionality. Mass is dependent on linear dimension cubed while surface effects depend on linear dimension squared. Hence volume effects are small at small scale and surface effects dominate. This is why insects can walk on water etc. On a supramolecular scale, surface effects totally dominate over mass effects.

If the wave were three dimensional then a spherical object would interact with a larger surface area of membrane while it is located in the concave region at the trough of the wave. At the peak of the wave, where the membrane would be convex, either the interacting surface area will be smaller or the membrane will be deformed to fit the particle. My calculations made the latter assumption but either way, the particle's interaction with the wave will produce an energy difference between the peak and the trough. That energy differrence arises from the way the particle interacts with the surface of the geometric wave and has nothing to do with gravity.
 
John Hewitt said:
I am sorry you feel that my reply did not meet your specifications. Nonetheless, I feel I made my opinion clear.
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Is it your opinion that the manufacturers of homoeopathic "medicines" should be allowed to make misleading claims about the efficacy of their products? You didn't make this clear in the other thread.
 
The use of the word "wave" to describe several different phenomena may be misleading. Might I suggest substituting the term "ripple" in the case of physical (ie surface distortion) waves?

Trying to imagine this process, I think of macroscopic examples.

1. The caterpillar track model - as in a tank or bulldozer. A lump of mud on a tank track will be carried forward along the upper surface, ("forward" being the direction of travel of the tank)- so both tank and mud move in the same direction, though at different velocities. This is true of all wheel-like rotation.
2. The "true" caterpillar ( let's call it "centipede") model, where a rythmic pulsation of legs causes a vertical hump to propagate along the animal's back. From memory, the hump moves forward, so the direction of movement of a free particle on the creature's back would depend on the precise timing and position of the particle in relation to the position and timing of the hump. (This might also be true of a tank track of the early World War 1 type, where the upper surface sloped significantly).

Hmm. Are macromechanical models relevant at all? A litre of water deforms as a Newtonian fluid: A drop of water is dominated by surface tension. How does a particle move on the surface of a moving drop of water? I would guess that it again depends critically on timing and position, with added complications of surface tension and charge distribution. It will certainly move, but is there any need of a single mechanism?

How rigid is the outer surface of a cell? Does it flow like a glacier? Does the whole cell pulsate? Do cells have a distinct "top and bottom?"

Damn. I love it when my whole worldview flips.

Lay on Mr. Hewitt.
 
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I have been otherwise engaged for the day but, even at this late Saturday hour, I shall now come back to your question 3.
What relevance has this to cells in multicellular organisms? The reason I ask this is that the model seems to propose that macromolecular cell membrane elements are moved around by physical waves in the cell membrane. Ocean waves cause objects to surf because they interact with the force of gravity. I don't see what force acts as the equivalent to gravity in a 3-dimensional block of cells with surfaces at all orientations.

The body of this question seems very concerned about gravity and, for that, you are referred to previous answers. The phenomena we are discussing are cell biological and concern the properties of single cells but they are rlevant to multicellular systems. The simplest cells to display such behaviour may be the prokaryotes, such as oscillatoria which form long chains of blue green algae cells and which are named for their behaviour. Their morphology seemed to appear very soon after the earth's formation. A number of the protozoa have striking wave patterns as propulsive mechanisms, paramecium being a ciliated example.

The whole issue of cell waves is deeply linked to the properties of multicellular organisms and wave phenomena are much better documented for larger organisms than they are for single cells and you can just work your way up. I believe Leeuwenhoek reported seeing waves through his first very first microscope and they are quite easy to see on small ciliates. Numerous invertebrates move or swim by wave mechanisms, and wave driven peristalsis underlies many physiologically important aspects of our own bodies, such as transport of food through the gut.

On a cellular level, such cohesive wave activities imply waves moving from cell to cell, so data flows from cell to cell. In general waves involve the transfer of energy without the transport of matter but these energy flows can form the basis for data flows. In other words, cells communicate with one another via waves. Hence, one sees reports that calcium waves pass through whole sheets of various epithelial tissues. Likewise, nerve impulses are cell surface waves. These are well known phenomena, books are written on them.

This, really, is the evolutionary and developmental context of the wave model. Proposing that there are waves on motile cells seems to me a reasonable suggestion. I invite readers to consider this for themselves. Do you, the reader, look at the suggestion that there are waves on cells and immediately think, "how could anybody make such a stupid suggestion?"

Also, consider the membrane flow model, discussed earlier. I do not know of a ssingle organism or cell type that moves by circulating its entire outer surface. So, now consider the proposal that cells move because their entire outer surface circulates. Forget about evidence for now, just ask yourself, a priori, "which theory the flow model or the wave model seems more likely to you?" To my mind, the wave model is clearly more likely to be true, though I accept that there remains a question of evidence.

Shortly, we will be able to discuss some of the answers to that question some of the worlds most distinguished scientific experts seem to hold in answer to that question.
 
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