The prevailing model of the mechanical function of intermediate filaments in 
cells assumes that these 10 nm diameter filaments make up networks that behave 
as entropic gels, with individual intermediate filaments never experiencing 
direct loading in tension. However, recent work has shown that single 
intermediate filaments and bundles are remarkably extensible and elastic in 
vitro, and therefore well-suited to bearing tensional loads. Here we tested the 
hypothesis that the intermediate filament network in keratinocytes is extensible 
and elastic as predicted by the available in vitro data. To do this, we 
monitored the morphology of fluorescently-tagged intermediate filament networks 
in cultured human keratinocytes as they were subjected to uniaxial cell strains 
as high as 133%. We found that keratinocytes not only survived these high 
strains, but their intermediate filament networks sustained only minor damage at 
cell strains as high as 100%. Electron microscopy of stretched cells suggests 
that intermediate filaments are straightened at high cell strains, and therefore 
likely to be loaded in tension. Furthermore, the buckling behavior of 
intermediate filament bundles in cells after stretching is consistent with the 
emerging view that intermediate filaments are far less stiff than the two other 
major cytoskeletal components F-actin and microtubules. These insights into the 
mechanical behavior of keratinocytes and the cytokeratin network provide 
important baseline information for current attempts to understand the 
biophysical basis of genetic diseases caused by mutations in intermediate 
filament genes.