Hagfish Slime Threads - The Functional Fold: Amyloid Structures in Nature - page 29

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reinforce -keratins (like wool), cell biologists have assumed that

the mechanical properties of intermediate filaments in living cells
can be approximated by the material properties of wool.

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This
assumption was seriously challenged, however, when it was shown
that the bundle of intermediate filaments that make up slime threads
are far more compliant and extensible than wool fibres.

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This result
raised two novel hypotheses—that intermediate filaments in cells
are far softer and more extensible than previously assumed, and that
the intermediate filaments in hard

-keratins like wool are modified
in some way to make them stiffer and less extensible.
The first hypothesis regarding the mechanics of intermediate
filaments in living cells makes a few critical predictions about how
the intermediate network in living cells responds to mechanical
stress. Specifically, if intermediate filaments in cells behave like
slime threads, they should be able stretch to elastically to strains
as high as 35%, and should resist breaking up to strains as high
as 220%. Furthermore, strains greater than 35% should result in
plastic deformation of the intermediate filament network. Testing
these predictions requires subjecting cells to strains much higher
than they typically experience in an experimental setting.
We are currently testing these predictions using a stable line of
human keratinocytes that expresses a fluorescently tagged version
of the intermediate filament gene keratin 14. Thus far, all of the data
we have collected using a custom-built uniaxial cell stretching device
is consistent with the predictions of this new model of intermediate
filament mechanics in living cells.

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Furthermore, we have found that
cells subjected to these extreme degrees of uniaxial strain remain
viable, which underscores the potential physiological relevance of
the elasticity and high extensibility of intermediate filaments. These
results also suggest the possibility that intermediate filaments could
be transformed into amyloid-like structures in cells after extreme
cellular deformations. The implications of this possibility will be
discussed in the concluding section of this chapter.
Further evidence for this model has come from recent in vitro

studies of the behaviour of single intermediate filaments probed
using atomic force microscopy (AFM). Kreplak and colleagues have
found that single intermediate filaments can be stretched with an
AFM tip to strains as high as 250% before breaking, and they are
currently in the process of attempting to derive the tensile stress-
strain curve for a single intermediate filament using these same