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Author
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Topic: Pollack's "Cells, Gels, and the Engines of Life"
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James A. Barham
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Member # 50
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posted 17. May 2002 10:11
I would like to create a thread for discussion of a fascinating and seminal new book that was recently drawn to my attention: Gerald H. Pollack's "Cells, Gels, and the Engines of Life" (Seattle: Ebner & Sons, 2001). (BTW, I thank the person who e-mailed me about this book from the bottom of my heart---unfortunately, I seem to have deleted your e-mail and cannot remember your name!)
Pollack has a revolutionary theory that almost all functional action in the cell can be understood in terms of phase transitions propagating along protein macromolecular structures. The key insight is that proteins create ordered (according to M.-W. Ho liquid crystal) structures in the vicinal water, and that phase transitions propagate as waves of disordering and reordering of the vicinal water.
This is a beatiful concept, which is very powerful and unifies a great many things in cell biology. Best of all, from my point of view, it dovetails beautifully with ideas by Ho, Vitiello and others (whom Pollack does not discuss) about macroscopic quantum coherence in the cell. Reading Pollack, I had the constant feeling of things coming together in an elegant and powerful way.
Obviously, this is still preliminary and will be highly controversial, since it overturns very many established views. The main thing that is distinctive about his view is that it places the forces driving motion directly in the large structures (actins, tubulins, etc.), and reinterprets the so-called "motor proteins" (kinesins, dyneins, etc.) as triggers.
Unfortunately, Pollack does not discuss the structure of most concern to us here at ISCID---the bacterial flagellum. He does lay out a convincing case for his model applying to the axoneme of the eukaryotic flagellum, but that is of course a very different structure. There are a number of apparent obstacles in the way of applying his ideas to the bacterial case (no kinesin triggers, no bound nucleotides for energy, etc.). But there are still a lot of gaps in our understanding of the bacterial flagellum (e.g., it is generally admitted, I believe, that the postulated proton-motive force driving the M ring "motor" is not well understood). Therefore, it is still possible that our current conception of the bacterial flagellum is wrong, and that Pollack's ideas may be vindicated even here.
Anybody else out there read Pollack yet? If so, what do you think?
[ 17 May 2002, 10:14: Message edited by: James A. Barham ]
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Rex Kerr
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Member # 632
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posted 29. September 2003 21:38
I've read the book in some detail. While he may have a point for certain systems, he spends most of his time talking about neurons, which I happen to know something about. His approach fails to explain quite a lot of data, including, most critically, the great degree of correlation between single channel properties and action potential shape. (Also, as I recall, he'd predict that perforated patches don't work at all, or would look like extracellular recordings, when in fact they look like intracellular recordings as the standard model predicts.)
Anyway, interesting, but at least partly wrong. I don't have the background to tell how much could be right, so I'm limited to rejecting the theory where I know that the data doesn't match. It certainly sounds very plausible in the areas that I am unfamiliar with. Then again, I thought it sounded pretty plausible with neurons until I brought to mind the details.
[ 29. September 2003, 21:39: Message edited by: Rex Kerr ]
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Nel
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Member # 614
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posted 30. September 2003 13:29
Rex writes:
quote:
His approach fails to explain quite a lot of data, including, most critically, the great degree of correlation between single channel properties and action potential shape.
Rex, since you read the book in some detail, could you explain why you think that he fails to explain this?
Rex writes:
quote:
Also, as I recall, he'd predict that perforated patches don't work at all, or would look like extracellular recordings, when in fact they look like intracellular recordings as the standard model predicts.)
Where does he predict that perforated patches don't work at all or that they look like extracellular recordings?
[ 30. September 2003, 13:37: Message edited by: Nelson-Alonso ]
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Rex Kerr
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posted 01. October 2003 01:19
In his model, voltages that you measure are the result of electrostatic effects from the protein gel that fills the cytosol of a cell. The membrane is almost irrelevant.
A perforated patch makes small holes in the membrane but doesn't actually stick an electrode inside the cell. Pollack (who is really just regurgitating the theory of someone else, whose name I can't remember but is heavily referenced in the book) would have to predict that a perforated patch electrode would record the same thing as an extracellular electrode, since it's not actually inside the gel that produces all the nifty effects. The conventional model says that the holes are enough to equalize the potential inside and outside the cell, and thus you'd record what looks like an intracellular potential.
Perforated patch recordings look like other intracellular recordings. You can find thousands of articles demonstrating this.
Also, Pollack goes on at some length about how single channel recordings don't really have much to do with whole cell currents, and that you can get activity that looks like a single channel just by patching onto a bit of rubber or something.
Well, that's nice, except for the extensive experiments that show that single channel statistics predict the shape of whole cell currents to an extraordinarily high degree of accuracy. If it isn't voltage-gated ion channels opening up and changing the potential in the expected and measured way, why the correlation?
That's what I remember anyway. (Also, some of the motivation comes from an intuition that the normal leaky method of mantaining potential is too expensive energetically, without really doing the calculation to see how much energy it is. When you do the calculation, you find out that it's actually okay, and in the ballpark of what you might expect.)
Like I said, I'm not an expert on all the areas Pollack touches. All I can say is that in the areas I don't know well, his theory sounds very reasonable, and in the areas I do know well, his theory sounds very reasonable but doesn't match the data, so most likely is incorrect in that aspect.
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Nel
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posted 01. October 2003 21:43
Rex writes:
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and in the areas I do know well, his theory sounds very reasonable but doesn't match the data, so most likely is incorrect in that aspect.
This is what is confusing me. What do you mean that in the areas you do know well, it "doesn't match the data"? So far all you have pointed to is how some models assume various properties, and you seem to imply that they are largely sucessful. However, this is irrelevant, even if true, to whether Pollack's view is correct or incorrect.
Some research has shown that the action potential brings along with it a "swelling" of the gel beneath the membrane: Tasaki I. Rapid Structural Changes in Nerve Fibers and Cells Associated with Their Excitation Processes Jpn J Physiol 1999, 49, 125-138. It is this observation that lead to some of the hypothesis in Pollack's book. This has been pointed to as recently as last year:
source
Of course the obvious next step, is to start experimenting with the connection between the gel and the potential itself. This is the type of data that would make headway into whether the theory is correct/incorrect.
[ 01. October 2003, 22:08: Message edited by: Nelson-Alonso ]
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Rex Kerr
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posted 01. October 2003 22:27
I posted two widely made observations that do not match predictions made by Pollack's model.
They are accounted for by current models.
I would hardly call this irrelevant. This is exactly how science is done. You compare multiple models with the data and see which one fits.
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Art
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Member # 179
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posted 01. October 2003 22:51
What's that adage about a picture's worth?
This one shows fairly respectable diffusion inside a cell. It's not consistent with a liquid crystalline state inside the cell (although it doesn't argue against very small, localized patches). 
Basically, a small patch of cell that contains a fluorescent protein is photobleached, and the diffusion of "active" protein into the bleached area measured as a function of time. No recovery can occur without diffusion, and very slow diffusion (orders of magnitude slower than seen in aqueous solution) necessitates an extended period of observation (much longer than that seen here).
A brief overview of the technique is here.
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Nel
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posted 01. October 2003 22:52
Rex,Art,
Pollack's model seems to predict that there would be large jumps in potential due to gel phase transitions. If this prediction bears out, would you still think that Pollack's model is incorrect?
[ 01. October 2003, 22:52: Message edited by: Nelson-Alonso ]
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Art
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posted 01. October 2003 23:34
quote:
Rex,Art,
Pollack's model seems to predict that there would be large jumps in potential due to gel phase transitions. If this prediction bears out, would you still think that Pollack's model is incorrect?
Yes. I am sure that one could generate phenomena akin to action potentials with contrived gel phase systems. But that's a far cry from relating this to real-life cells. Work with membranes and transport components (including genetic studies, I suspect) afford a more realistic perspective.
Pollack's ideas sound a lot to me like the ideas I came across in the 70's that argued that transport processes in cells were the results of a contrast in the properties of intra- and extra-cellular phases. This idea was soundly refuted with the demonstration of transport in membrane vesicles that were free of "cytosol" (among other demonstrations). The observations summarized by Rex, IMO, similarly render Pollack's ideas unnecessary as an explanation for the electrical properties of neurons.
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Nel
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posted 02. October 2003 00:24
Art writes:
quote:
The observations summarized by Rex, IMO, similarly render Pollack's ideas unnecessary as an explanation for the electrical properties of neurons.
All Rex did was pretty much outline what other models assumed (and what they predicted from those assumptions, as well as what he thinks Pollack would predict). It may be that they are correct (I am largely playing the devil's advocate in this thread). Sometimes it's easy to adjust the unknowns of a model to get what you want. The bottom line is that there is very limited information on the properties of the cytoskeleton/phase transition. Experiments such as those that I describe above can be done that illuminate the nature of phase transition.
[ 02. October 2003, 00:24: Message edited by: Nelson-Alonso ]
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Rex Kerr
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posted 02. October 2003 05:22
Like Nelson and Art said, "all" I did was summarize why Pollack's model fails to explain neuron properties, and that current models work well. There's not much room for devil's advocacy here.
I think I'm done with this thread.
[ 02. October 2003, 05:26: Message edited by: Rex Kerr ]
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zygotecowboy
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Member # 220
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posted 08. October 2003 18:53
A relevant review...
quote:
Selling cellular gels
Book review by Michael Klymkowsky
Nat Cell Biol. 2001 Sep;3(9):E213.
There is no denying it, cells are dauntingly complex—densely packed with macromolecules of many sorts interacting in myriad ways. In the past, cellular complexity had been subsumed in the term ‘protoplasm’. The modern revolution in molecular biology has, in large measure, been based on the resolution of protoplasm into discrete structures—surface and endogenous membrane systems, membrane-delimited organelles (for example, mitochondria, chloroplasts and the nuclei of eukaryotic cells) and their embedded proteins, cytoskeletal filament systems and their associated proteins, chromosomes and the gene regulatory/replicative machinery, and a host of specialized macromolecular machines or ‘somes’ such as ribosomes, proteosomes, splicesomes and foldosomes (chaperones).
Modern cell-biology textbooks typically deal with these cellular components as distinct topics. Occasionally, they may include a few of David Goodsell’s structurally realistic, but static drawings of cellular interiors, but they rarely deal with the dynamic realities of the living cell. It is a main thesis of Gerald Pollack’s Cells, Gels and the Engines of Life that this molecular reductionism is altogether too naive and has missed something crucial —namely, the role of water generally and how its structuring determines cellular organization and function more specifically. There is some truth in this view—we are still in the early stages of placing the molecular machines of the cell into a functionally realistic context.
This is, however, not a carefully reasoned and objective presentation of the state of our knowledge and its limitations. It is highly polemical work whose admitted goal is a revolution in our understanding of cellular organization and function. Its style is folksy and ‘us against them’ to the point of being almost anti-scientific. In fact, its overall style is reminiscent of creationist writings. Pollack focuses observations that appear, at least superficially, to be inconsistent with what he paints as the current dogma of the cell-biology establishment. On the basis of these inconsistencies he discards—more or less lock, stock and barrel—an extremely large number of well-established observations in favour of a few scattered and almost anecdotal ones. Given that biology is built on the cross-checked results of many investigators, this can be a misleading strategy. Membrane channels and pumps are the first to go, but they are by no means the last. They are replaced with models that are based primarily on structured water.
That protoplasm has the qualities of a crowded, thixotropic colloidal solution is well appreciated (see E. B.Wilson’s discussion of protoplasm in The Cell in Development and Heredity, Garland Publishing). That non-living colloids can display behaviours reminiscent of cells is also not in question. That modern textbooks generally ignore the fact that protoplasm behaves differently to a simple concentrated protein solution is also clear. That this implies that the view of the cell presented in the typical cell-biology textbook is fundamentally mistaken is, however, too broad a jump. More to the point, the author’s approach does injury to the ideals of scientific inquiry.
Cells are about 70% water and packed with macromolecular components. How is cellular water organized? Previous studies estimated that roughly 90% of total cellular water is present as free, rather than bound or structured water. Nevertheless, there are arguments, which are reflected in Pollack’s text (for example see http://www.consciousness.arizona.edu/hameroff/water2.html), that structured water is responsible for everything from membrane polarity to consciousness. Echoes of ‘polywater’ spring to mind.
What Pollack has done is collect a diverse set of observation that appear to fly in the face of the conventional view of cellular organization: these range from the apparent presence of channel-like electrical behaviour when microelectrodes are opposed to polymer surfaces and the maintenance of membrane potential when membranes are physically breached, to the movement of singleheaded kinesin-type motor proteins. This type of scientific ‘muck-making’ has a certain appeal, as it points out gaps in our knowledge that are often glossed over in textbooks. I, for one, have always been intrigued by the evidence that holes are routinely torn in the membranes of living cells by mechanical stresses.
Unfortunately, this is only the first step in developing a more sophisticated understanding of cellular processes. What Pollack fails to do is to bring an analytical and rigorous scepticism to these ‘heretical’ observations; moreover, he ignores much of what is already known. Consider his discussion of membrane channels: his basic premise is that their ability to conduct specific ions through a membrane is a “functionally insignificant” (page 21) by-product of their true role as “receptors”. But the ramifications of this view are very poorly developed, and there is essentially no serious consideration given to the many structural and functional observations that support the channel/pump hypothesis.
While pointing out that pure lipid bilayers are relatively impermeable to water, he dismisses as superfluous the recent characterization of water channels (aquaporins) as a solution to the observed permeability of biological membranes. Instead, he proposes that water leaks through membranes at the lipid/protein boundary layer. The data for water transport through aquaporins are never seriously considered.
There is a certain type of person who needs to turn the world upside down. As the boundaries of the mysterious disappear, this urge often grows stronger. As biology matures, it has become a study of the structure, regulation, function and interactions of molecular machines—and many of its mysteries have vanished. Pollack’s book seeks to recover some of that mystery.
Michael Klymkowsky is in the Department of
Molecular, Cellular and Developmental
Biology, University of Colorado, Boulder,
Colorado 80309-0347, USA.
e-mail: klym@spot.colorado.edu
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Nel
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posted 09. October 2003 00:23
Here is a more recent review:
quote:
There is a natural tendency for this to occur in laboratories where individuals try to prove rather than disprove their hypothesis; this is amongst the gravest of errors that can be made in scientific research. So, if you have ever written or uttered a phrase that expresses the sentiment
"Our work proves that [X] happnes because of [Y]", you really should consider obtaining a copy of Gerald Pollack's book.
Journal of Pharmacy and Pharmacology 55(6): 857-858 (2003)
[ 24. February 2006, 02:24: Message edited by: Nel ]
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