Propagation of Action Potential

[bernard]

Hello SomaSimplers,

http://www.ncbi.nlm.nih.gov/books/bookres.fcgi/mboc4/ch11f28.gif

This page comes from the Molecular cell ebook:
http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=mboc4.figgrp.2043

the picture comes from this chapter =>
http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=mboc4.section.2027

Of course, I do not think that it's a possible mechanism. It doesn't work but I have to show you, how, why and where!

[bernard]

The text below is brought from the cited page and shows that it exists 2 currents flows: an active (ions crossing the membranes via ions channels and a passive one, induced by cable property)
Myelination Increases the Speed and Efficiency of Action Potential Propagation in Nerve Cells
The axons of many vertebrate neurons are insulated by a myelin sheath (http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=mboc4.glossary.4754#5503), which greatly increases the rate at which an axon can conduct an action potential. The importance of myelination is dramatically demonstrated by the demyelinating disease multiple sclerosis, in which myelin sheaths in some regions of the central nervous system are destroyed; where this happens, the propagation of nerve impulses is greatly slowed, often with devastating neurological consequences.

Myelin is formed by specialized supporting cells called glial cells (http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=mboc4.glossary.4754#5232). Schwann cells (http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=mboc4.glossary.4754#5779) myelinate axons in peripheral nerves and oligodendrocytes (http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=mboc4.glossary.4754#5572) do so in the central nervous system. These glial cells wrap layer upon layer of their own plasma membrane in a tight spiral around the axon (Figure 11-30 (http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=mboc4.figgrp.2047)), thereby insulating the axonal membrane so that little current can leak across it. The myelin sheath is interrupted at regularly spaced nodes of Ranvier, where almost all the Na+ channels in the axon are concentrated. Because the ensheathed portions of the axonal membrane have excellent cable properties (in other words, they behave electrically much like well-designed underwater telegraph cables), a depolarization of the membrane at one node almost immediately spreads passively to the next node. Thus, an action potential propagates along a myelinated axon by jumping from node to node, a process called saltatory conduction. This type of conduction has two main advantages: action potentials travel faster, and metabolic energy is conserved because the active excitation is confined to the small regions of axonal plasma membrane at nodes of Ranvier

[Diane]

I think that glia, arising as they do from neural crest which is originally nerve cell, would be a very important secondary system, passing info along cell to cell through gap junctions, neurochemically. They do that in the brain as I recall, do you think they can do that across nodes out in the periphery? (Wouldn't it be interesting if it was determined that myalin has a signalling system? :rolleyes: )

[bernard]

Diane,

Your point of view makes sense and tell us that glia/myelin cells were forgotten in the riddle. This is a living point of view. :thumbs_up

I was thinking about more simple things. :embarasse

I'll try to bring facts and offer the Occam chainsaw 101 for your choice?

BTW, I use the Occam chainsaw but knew a razor? :embarasse

[bernard]

Perhaps the best proof available actually against the "cable theory".


J Cell Biol. (http://javascript%3Cb%3E%3C/b%3E:AL_get%28this,%20%27jour%27,%20%27J%20Cell%20Biol.%27%29;) 2005 May 9;169(3):527-38. Related Articles, (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Display&dopt=pubmed_pubmed&from_uid=15883201) Links (http://javascript%3Cb%3E%3C/b%3E:PopUpMenu2_Set%28Menu15883201%29;) http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--highwire.stanford.edu-icons-externalservices-pubmed-free-jcb-free.gif (http://www.ncbi.nlm.nih.gov/entrez/utils/lofref.fcgi?PrId=3051&uid=15883201&db=pubmed&url=http://www.jcb.org/cgi/pmidlookup?view=long&pmid=15883201)
Tight junctions in Schwann cells of peripheral myelinated axons: a lesson from claudin-19-deficient mice.

Miyamoto T (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Miyamoto+T%22%5BAuthor%5D), Morita K (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Morita+K%22%5BAuthor%5D), Takemoto D (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Takemoto+D%22%5BAuthor%5D), Takeuchi K (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Takeuchi+K%22%5BAuthor%5D), Kitano Y (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Kitano+Y%22%5BAuthor%5D), Miyakawa T (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Miyakawa+T%22%5BAuthor%5D), Nakayama K (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Nakayama+K%22%5BAuthor%5D), Okamura Y (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Okamura+Y%22%5BAuthor%5D), Sasaki H (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Sasaki+H%22%5BAuthor%5D), Miyachi Y (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Miyachi+Y%22%5BAuthor%5D), Furuse M (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Furuse+M%22%5BAuthor%5D), Tsukita S (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Tsukita+S%22%5BAuthor%5D).

Department of Cell Biology, Graduate School of Medicine, Kyoto University, Japan.

Tight junction (TJ)-like structures have been reported in Schwann cells, but their molecular composition and physiological function remain elusive. We found that claudin-19, a novel member of the claudin family (TJ adhesion molecules in epithelia), constituted these structures. Claudin-19-deficient mice were generated, and they exhibited behavioral abnormalities that could be attributed to peripheral nervous system deficits. Electrophysiological analyses showed that the claudin-19 deficiency affected the nerve conduction of peripheral myelinated fibers. Interestingly, the overall morphology of Schwann cells lacking claudin-19 expression appeared to be normal not only in the internodal region but also at the node of Ranvier, except that TJs completely disappeared, at least from the outer/inner mesaxons. These findings have indicated that, similar to epithelial cells, Schwann cells also bear claudin-based TJs, and they have also suggested that these TJs are not involved in the polarized morphogenesis but are involved in the electrophysiological "sealing" function of Schwann cells.

PMID: 15883201 [PubMed - indexed for MEDLINE]


Here is the pdf file =>
www.somasimple.com/pdf_files/tight_junctions.pdf (http://www.somasimple.com/pdf_files/tight_junctions.pdf)

[bernard]

Hi All,

The most important pieces of the previous paper are below.

[bernard]

I'll add this lovely old piece (I'll give the author later).
It explains what is the saltatory conduction and precisely the two phases its exists (?) during the process.

We musn't forget that a myelinated neuron begins its life without myelin. It acts in its early life as an unmyelinated one.

[Diane]

Besides, in the ganglion, myelin becomes completely irrelevant; it's an orgy of intercommunication in there, according to Grieve's (see post #18) (http://www.somasimple.com/forums/showthread.php?t=2426).

[bernard]

Absolutely Diane,

Myelin enhances only the speed of communication.
I just wanted to point out the origin of electrical behaviour in axons. The paper was written in 1950 but remains (for me) the trigger of misunderstandings about this perfect thing that is neuron.

The previous attachments are saying that removing tight junctions (a physical proterty = tightness) from axons creates loose myelin which gives delayed action potentials. If meylin was really an electrical insulator, removing tight junctions will have no effect.

So the electrical theory fails, once again, to fit the fact.

[bernard]

I think that you'll like this one, Diane? It fits your "tunneling" theory.
Unmyelinated fibres have a physical travelling wave during APs.
Good news for fluid things!


Biophys J. (javascript:AL_get(this, 'jour', 'Biophys J.');) 1990 Mar;57(3):633-5. Related Articles, (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Display&dopt=pubmed_pubmed&from_uid=2306506) Links (javascript:PopUpMenu2_Set(Menu2306506);) http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--www.ncbi.nlm.nih.gov-corehtml-query-pubmed-pmc.gif (http://www.ncbi.nlm.nih.gov/entrez/utils/lofref.fcgi?PrId=3494&uid=2306506&db=pubmed&url=http://www.pubmedcentral.gov/articlerender.fcgi?tool=pubmed&pubmedid=2306506)
Volume expansion of nonmyelinated nerve fibers during impulse conduction.

Tasaki I (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Tasaki+I%22%5BAuthor%5D), Byrne PM (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Byrne+PM%22%5BAuthor%5D).

Unit on Neurobiology, National Institute of Mental Health, Bethesda, Maryland 20892.

Nonmyelinated nerve fibers undergo rapid volume expansion while carrying an impulse. This volume expansion is incurred as a consequence of a lateral expansion of the excited portion of the fibers, where the superficial layer is transformed into a low-density structure.

PMID: 2306506 [PubMed - indexed for MEDLINE]

[Diane]

Interesting.. like a bolus through a python. Biomechanics of neurons? :)

[bernard]

Or like a limb of an amoeba. Nature uses and reuses the same useful tips. Just with changed scales.

Neuron is a mobile cell.

[Diane]

At least that growth cone sure is.. like a pitbull on a leash who smells raw steak...

[bernard]

http://www.somasimple.com/flash_anims/ap_001.swf


action potential 001 (http://www.somasimple.com/flash_anims/ap_001.swf)

[Diane]

Non-myelinated nerve fibres undergo rapid expansion... makes me see a picture in my head of a bulge moving down a garden hose, bolus in a python, etc. Is the myelin there to "contain" bulges, smooth them out? Make it harder for them to "bulge"? Does "bulge transport" move faster in a stiffer pipe than it does in a flexible one? It makes sense on first take, just that physically surrounding a tube would change the deformability of that tube..however..

About myelin being an active communicator rather than a buttress, and definitely instead of it being a "nurse cell", I found a clue in one of Kevin McHenry's latest essays: (http://www.painonline.com/mt-archives/2006/06/what_is_inflamm.html#more)
He discusses white blood cellls and their role in inflammation, then adds this:
Last of all we come to the glia, which surround neurons, which used to be called "supportive cells" by Dr. Frankensteins who had no idea what glia actually were doing there. We now know that glia perform no structural role whatsoever and therefore cannot be "supportive". The latest word is that these cells are involved in inflammation, neuroinflammation to be specific. They spit out materials too, such as growth factors, which cause the genes of pain neurons to go postal (hog wild) and take over the protein factories in the genes which make acids. Eeeeeeeyew. That would be why axons get AIGS's. For the longest time I had in my head the idea that glia and Schwann's buffered the axons, kept them "clothed", kept them "insulated".. (to be fair, McHenry is not talking peripherally, only centrally. Maybe Schwann's are functionally distinct from glia somehow...)

Sorry, off track now. Back to axon bulges Bernard. :)

[bernard]

Is the myelin there to "contain" bulges, smooth them out? Make it harder for them to "bulge"? Does "bulge transport" move faster in a stiffer pipe than it does in a flexible one?

I'll make some visual propositions but you understood the principle but you're now, contesting the traditional point of view and theory.

[bernard]

For the longest time I had in my head the idea that glia and Schwann's buffered the axons, kept them "clothed", kept them "insulated"..

Keep this in your mind for the moment! ;)

[bernard]

makes me see a picture in my head of a bulge moving down a garden hose, bolus in a python, etc.

A very huge difference however. Nothing in an axon really move forward. Ions move vertically and disturb the shape and this bulging is recreated a bit further. No material travels as the action potential does.

That is all the beauty of the solution. :thumbs_up

[Diane]

On the sailing moving thread, there is a window showing a wave simulator (http://www.nationalgeographic.com/volvooceanrace/interactives/waves/index.html). You can click on a small menu in that window labelled "water particles" that shows how the water doesn't really go anywhere, that the particles roll over each other to permit the wave to pass through them. That is in free, unbound, ocean water of course, and the waves are, as we know, (those of us whose vestibular nervous systems become disordered enough to end up queasy), BIG.

Inside an axon, which is a very thin structure, is there enough room for such a possibility? Is the axonal substance/liquid "unbound" enough, and while there is axonal transport of this and that, is there room for wave propagation via "water" particles/molecules rolling?

[bernard]

Yes, Diane the membrane structure is deformed as a wave is.

[Diane]

But, do axonic particles "roll"?

[bernard]

Diane,

It is possible but at this atomic/molecular level, it has less sense.
And if water molecules are involved, for sure, the real forces remain invisible => attraction and repulsion. It is why the system is much more than a sea wave.

[Diane]

That's what I thought.

[bernard]

this summary comes from this page

http://en.wikipedia.org/wiki/Action_potential
It's one of the best and clear definition sequence of the action potential.

The action potential

When a stimulus arrives at a receptor or nerve ending, its energy causes a temporary reversal of the charges on the neuron cell surface membrane. As a result, the negative charge of 70 mV inside the membrane becomes a positive charge of around +40mV. This is known as the action potential, and in this condition the membrane is said to be depolarised. (See depolarization (http://en.wikipedia.org/wiki/Depolarization)) This depolarization occurs because channels in the axon membrane change shape, and hence open or close, depending on the voltage across the membrane. They are therefore called voltage-gated ion channels (http://en.wikipedia.org/wiki/Voltage-gated_ion_channel). The sequence of events is described below.
At resting potential some potassium leak channels (http://en.wikipedia.org/wiki/Resting_ion_channel) are open but the voltage-gated sodium channels (http://en.wikipedia.org/wiki/Sodium_ion_channel#Voltage_gated_sodium_channels) are closed. Potassium diffusing down the potassium concentration gradient creates a negative-inside membrane potential.
A local membrane depolarization caused by an excitatory stimulus causes some voltage-gated sodium channels in the neuron cell surface membrane to open and therefore sodium ions diffuse in through the channels along their electrochemical gradient. Being positively charged, they begin a reversal in the potential difference across the membrane from negaitve-inside to positive-inside. Initially, the inward movement of sodium ions is also favored by the negative-inside membrane potential.
As sodium ions enter and the membrane potential becomes less negative, more sodium channels open, causing an even greater influx of sodium ions. This is an example of positive feedback. As more sodium channels open, the sodium current dominates over the potassium leak current and the membrane potential becomes positive inside.
Once a membrane potential of around +40 mV has been established, voltage-sensitive inactivation gates of the sodium channels, sensitive to the now positive membrane potential gradient, close (so further influx of sodium is prevented). While this occurs, the voltage-sensitive activation gates on the voltage-gated potassium channels (http://en.wikipedia.org/wiki/Potassium_channel#Voltage_sensitive_channels) begin to open.
As voltage-gated potassium channels open and there is a large outward movement of potassium ions driven by the potassium concentration gradient and initially favored by the positive-inside electrical gradient. As potassium ions diffuse out, this movement of positive charge causes a reversal of the membrane potential to negative-inside and repolarisation of the neuron back towards the large negative-inside resting potential.
The large outward current of potassium ions through the voltage-gated potssium channels causes the temporary overshoot of the electrical gradient, with the inside of the neuron being even more negative (relative to the outside) than the usual resting potential. This is called hyperpolarisation (hyperpolarization (http://en.wikipedia.org/wiki/Hyperpolarization)). The voltage-sensitive inactivation gates on the potassium channels now close and the continual movement of potassium through potassium leak channels again dominates the membrane potential. Sodium-potassium pumps continue to pump sodium ions out and potassium ions in, preventing any long-term loss of the ion gradients. The resting potential of -70 mV is re-established and the neuron is said to be repolarised.I just reproduced fact in the animation below. Hope that some of you will see the contradiction created with the figure in the first post?!
Look at the point 16: You're an incoming positive ion! What are you seeing at your left and on your right?

http://www.somasimple.com/flash_anims/ap_002.swf

[bernard]

ps: You are seeing only the 3 first points of the description.

I bolded some lines, showing the possible electrostatic forces that come with the membrane crossing.

Actually you viewing a little patch of membrane. It is not possible to record such events.

All the scene is taken in real time that lasts as you're watching the movie.

I "froze" the scene at the end. Normally the wave will run and continue its travel.
It shows that an AP exists in its whole length during the travel. And if it exists then all points that are its structure must exist too. We are tehn able to see/consider the possible theory behind its existence.

[BB]

Hi Bernard,
Is the difference you are pointing out between the 2 pictures,
-instead of pulsing waves, like seen in a heart monitor, passing down one after the other
-It's a smooth flowing gradual building and declining wave?

Cory

[flaviovitor]

Dear Bernard,

I am not understand some points of your theory, but I intend to do it. Besides, I want to participate in this complex process of MEMBRANE RESTING POTENTIAL and ACTION POTENTIAL.

So, I found a software which can help you somehow, despite I have not downloaded it for myself. The link is:http://neuronsinaction.com/ (NEURONS IN ACTION).

But, my most important intention here, is to suggest you that this enterprise could finance your research or project.

Cheers from Brazil,


Flávio.

[bernard]

Flavio,

Forget this link. It is the worst explantion I found about neuron. That the theory I'm against.

Cory,

Your second point is perhaps closer.

Imagaine you're at a train station and looking at running trains.

Action potentials are trains that take passengers without stoping.
And the most funny is that passengers are going in and out the wagons at the same speed that train is travelling.
And the first wagon take only x passengers, the seond takes x+y, and so on, until the middle wagon that carries the most passengers.
then all passengers are going out in a similar sequence.

The thickness of the line is a bit like the number of our positive passengers.

My animation based upon facts, rejects the picture of the first post because they create a backward current of "passengers" that is not allowed neither possible.

[bernard]

Maybe my story with this fool train and its mad passengers remains unclear.

Here another metaphor:
Imagine that you have some annular/ring-shaped ballons. Let's suppose they are glued together forming a tube.

At the resting position, all ballons are quite empty.
There is a subtle mechanism that permits the ballon inflating. It follows these rules:


It acts on the next ballon.
It starts when a treshold pressure is reached.
It stops obviously when the air reserve is consumed.
When all air is consumed, the system deflates.
If the system is running, you will see that left ballon is inflating, pushing to the right the next one, then the next inflates pushing the next right one and while the left one deflates.
You have a a moving and travelling air wave with a restricted allowed direction => inflated ballons do not allow backward propagation.

[Diane]

Nice image. :)

[bernard]

Hi all,

I started some fierce and critical thinking on biology forums:
this one seems to have ended?
http://www.sciencechatforum.com/bulletin/viewtopic.php?t=1742
So I began another one:
http://www.physicsforums.com/showthread.php?t=124255
Hope I will get some responses?

And I added a little question there =>
http://en.wikipedia.org/wiki/Talk:Action_potential

[bernard]

I'm not quite sure then I understand what you are asking, the principles underlying passive propagation along the axon are the same with or without myelin. With myelin, the only difference is that Rm is larger and Cm is smaller, leading to a longer legth constant and a faster time constant. From these values you can calculate the rate of change in Vm at a given distance and time from the current source, be that a node with Na+ channels or an artificial current injection. This should explain the delay between nodes. The first 2 refs should address this, but also look at the textbook since it will summarize years of work into a cohesive picture. Nrets (http://en.wikipedia.org/wiki/User:Nrets) 18:44, 24 June 2006 (UTC)

Hi all,

I'm discussing about possible condradictions in the AP propagation on the Wikipedia site. The reponse given above was a revelation. I knew that something was wrong and I knew that Nature was more subtle than our big hands on this marvelous cell: neuron.

Yerterday, I found the proof.

Imagine that Action potential is a solar car (ions are mimicking the sun). I can understand that when the sun is lighting my car, my car can travel.
But In the original theory, they are simply saying that if the car enters a long tunnel, the car goes faster. What a smart car! But Nature doesn't make miracles. Nature used a different mean as I thought.

[bernard]

Phys Rev Lett. (javascript:AL_get(this, 'jour', 'Phys Rev Lett.');) 2006 Feb 3;96(4):048104. Epub 2006 Feb 2. Related Articles, (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Display&dopt=pubmed_pubmed&from_uid=16486900) Links (javascript:PopUpMenu2_Set(Menu16486900);) http://www.ncbi.nlm.nih.gov/entrez/query/egifs/-PMGifs-Toolbar-topub.gif (http://www.ncbi.nlm.nih.gov/entrez/utils/lofref.fcgi?PrId=3068&uid=16486900&db=pubmed&url=http://link.aps.org/abstract/PRL/v96/p048104)
Osmotically driven shape transformations in axons.

Pullarkat PA (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Pullarkat+PA%22%5BAuthor%5D), Dommersnes P (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Dommersnes+P%22%5BAuthor%5D), Fernandez P (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Fernandez+P%22%5BAuthor%5D), Joanny JF (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Joanny+JF%22%5BAuthor%5D), Ott A (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Ott+A%22%5BAuthor%5D).

Experimentalphysik I, University of Bayreuth, D-95440, Bayreuth, Germany.

We report a cylindrical-peristaltic shape transformation in axons exposed to a controlled osmotic perturbation. The peristaltic shape relaxes and the axon recovers its original geometry within minutes. We show that the shape instability depends critically on the swelling rate and that volume and membrane area regulation are responsible for the shape relaxation. We propose that volume regulation occurs via leakage of ions driven by elastic pressure, and analyze the peristaltic shape dynamics taking into account the internal structure of the axon. The results obtained provide a framework for understanding peristaltic shape dynamics in nerve fibers occurring in vivo.

PMID: 16486900 [PubMed - indexed for MEDLINE]

[bernard]

Ann Biomed Eng. (javascript:AL_get(this, 'jour', 'Ann Biomed Eng.');) 2005 Mar;33(3):376-82. Related Articles, (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Display&dopt=pubmed_pubmed&from_uid=15868728) Links (javascript:PopUpMenu2_Set(Menu15868728);) http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--production.springer.de-OnlineResources-Logos-springerlink.gif (http://www.ncbi.nlm.nih.gov/entrez/utils/lofref.fcgi?PrId=3055&uid=15868728&db=pubmed&url=http://www.springerlink.com/openurl.asp?genre=article&issn=0090-6964&volume=33&issue=3&spage=376)
Substrate curvature influences the direction of nerve outgrowth.

Smeal RM (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Smeal+RM%22%5BAuthor%5D), Rabbitt R (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Rabbitt+R%22%5BAuthor%5D), Biran R (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Biran+R%22%5BAuthor%5D), Tresco PA (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Tresco+PA%22%5BAuthor%5D).

Keck Center for Tissue Engineering, Department of Bioengineering, University of Utah, Salt Lake City, UT 84112, USA.

Nerve outgrowth in the developing nervous system utilizes a variety of attractive and repulsive molecules found in the extracellular environment. In addition, physical cues may play an important regulatory role in determining directional outgrowth of nervous tissue. Here, by culturing nerve cells on filamentous surfaces and measuring directional growth, we tested the hypothesis that substrate curvature is sufficient to influence the directional outgrowth of nerve cells. We found that the mean direction of neurite outgrowth aligned with the direction of minimum principle curvature, and the spatial variance in outgrowth direction was directly related to the maximum principle curvature. As substrate size approached the size of an axon, adherent neurons extended processes that followed the direction of the long axis of the substrate similar to what occurs during development along pioneering axons and radial glial fibers. A simple Boltzmann model describing the interplay between adhesion and bending stiffness of the nerve process was found to be in close agreement with the data suggesting that cell stiffness and substrate curvature can act together in a manner that is sufficient to direct nerve outgrowth in the absence of contrasting molecular cues. The study highlights the potential importance of cellular level geometry as a fidelity-enhancing cue in the developing and regenerating nervous system.

Publication Types:
Evaluation Studies (javascript:AL_get(this, 'ptyp', 'Evaluation Studies');)
Validation Studies (javascript:AL_get(this, 'ptyp', 'Validation Studies');)
PMID: 15868728 [PubMed - indexed for MEDLINE]