On Sun, 6 Feb 2000 hal@finney.org wrote:
>
> I am concerned about synaptic structure.
Actually, if you think about it, there may be very little extracellular
material holding synapses together, unlike say an extracellular matrix
in many other tissue types. This is probably due to the fact that
the neurotransmitters have to diffuse across these regions. Taking
a look at The Molecular Biology of the Cell, Chapter 19, synapses
seem to have a size of 0.5-1.0 micrometer (so these are roughly
the size of nanobots, which is pretty big). This makes sense because
the axon terminals have to contain mitochondria to generate energy
to drive neurotranmitter manufacture and recycling. MBotC also notes
that synapses have "thickened" postsynaptic and to a lesser extent
presynaptic membranes. The presynaptic membranes have behind
them large numbers of neurotransmitter vesicles, while the post-synaptic
membranes presumably have large numbers of neurotransmitter gated
ion channels in them. So recognition of the synapses should be
straight forward. Then the question comes down to what keeps this
structure in place. That would seem to fall on the shoulders of the
microtubules and intermediate filaments within the axon itself.
Tracing the paths and lengths of these filaments would seem to
dictate exactly where an axon should end up in 3D space. The
pattern of these filaments within the axon has to be fairly
unique and so even if an axon is severed entirely, you should
be able to find its opposite face with the nearby material
simply by matching filament patterns.
If there is some extracellular matrix surrounding a synapse
(perhaps useful for keeping the neurotransmitters from diffusing
too much) then that provides an additional set of mirror images that
you can use to match up surfaces.
> I don't know how rigidly the synapse is held together, but I suspect
> that a growing ice crystal could separate, perforate and even shred
> the membranes.
That was my point, that crystals would presumably disrupt hydrogen
bonds (dictating hydrophobic/hydrophilic interactions) before they
actually "broke" proteins.
> I would suspect that cell membranes are not strong enough to withstand
> ice crystal penetration.
Agreed, but membranes are self-healing if you put them in relative
proximity to each other. There are many experiments documenting
the movement of proteins in membrane surfaces unless they are fixed
to the internal filaments in some way. For cryonics recovery you
would have to have a large number of "membrane-healing" nanobots
that "covered" fractured membrane surfaces and patched or healed them.
Robert has a precedent for this in his "endotheliocytes" that collectively
do "plaque" dissection and repair in blood vessels.
Now, interestingly enough, since you are interested in keeping
as much of the external structure intact as possible, it might
make sense for the nanobots to operate from within the neurons.
Get into a neuron, remove the ice crystals and filaments as
necessary (tracking molecule counts and locations), when you
find some damaged membranes attach "bungy" proteins with
grappling hooks to the severed surfaces, so when you warm things up
they get drawn back together. Then back your way out, reinstalling
any removed molecules as necessary.
> I have the impression that synapses are relatively gently bound together.
I'm unsure, perhaps Anders knows. We could probably make some estimates
on this based on some research into the force required to cause
a concussion or permanent brain damage (say for professional fighters).
Then the question is whether growing ice crystals have this much
"force" or whether they are going to always grow along the path
of least resistance. It sould seem to me they should only grow
on surfaces where water is available. Once they grow to
a membrane, they should stop growing. Only growth on the
opposing face striking a similarly hard surface would seem to
be able to generate the force required to puncture membranes.
I think this is something that could use some molecular modeling.
But if you think about it, if you got too much membrane puncture
then when you thaw a steak or a fish you should get some kind
of icy steak/fish puree, not something by and large that looks like
the steak or fish that you froze. And food freezing is certainly a more
severe process than cryonic suspension.
> The problem is that the shapes may not match very well once the ice
> is removed. As the ice is forming, the material around it is at least
> a semi liquid. Water flows out of the cells and they would partially
> collapse due to dehydration. The cells themselves would be shoved
> around by the ice, tugged and torn, and their shapes will change.
True, but I don't think the shapes would change very much at
low temperatures. To lose the original structural pattern,
you would have to disassemble filaments, mitochondria, etc. and
those require chemical reactions that most likely cannot occur
(or at least don't occur rapidly on the scale of freeze-down time).
We know that because we can take the brain down to near-zero
and recover it. Now the deydration aspect is simply like that
of letting the air out of a oddly shaped balloon. When you
put the air back in, it returns to its original shape because
that is what is required by the surface areas. I think so
long as you heal the membrane surface, this should happen with
neurons as well, especially because of the internal skeleton.
Robert
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