I don't necessarily think that low temps have anything to do with denaturation.
Yes, if you can avoid replacing the solvent. But how do you avoid that, and still avoid creation of ice crystals? Actually, now that I think of it, there is a possible solution: expressing icefish proteins within neuronal cells. Of course, who knows shat they would do to neuronal physiology, and you can't really express them after death...
I'm not sure that less toxic cryoprotectants are really feasible. But yes, that would be a good step forward.
I actually think it's better to keep them together. Trying theoretical approaches as quickly as possible an
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