by PhilipJ on 22 August 2006
Wormlike chains do a reasonably good job at describing the force-extension relation for dsDNA, where at low forces the model reduces to a Hooke’s law form and at high forces a non-linear inverse square term describe the rapid increase in force as you start reaching the molecule’s contour length. At low forces you’re basically just removing the configurational entropy that a floppy polymer can have, and at high forces you’re starting to do work on the bonds holding the molecule together, but in all cases the form of the molecule stays the same, that of a isotropic rod.
Given that this is the model used to derive the wormlike chain, I have never been able to understand, then, why the people doing protein unfolding use wormlike chains to fit their data as well. A folded protein is nothing like an isotropic curled up rod, and configurational entropy has basically nothing to do with the folded structure.
The reason I’m thinking about this now is because there is an interesting paper in this week’s PNAS from the Rief lab building on the work AndrÃ© described from this year’s Biophysical Society meeting on the deformation response of single GFP molecules unfolded from different pairs of amino acids by atomic force microscopy (subscription required). The directions accessible to them are shown here:
As stated in their conclusions, ”[a] richness of of behaviors with widely varying unfolding forces and various directional spring constants could be observed for the case of GFP”, and carrying out similar studies on the myriad of protein types will surely lead to further exciting results in the future. My only complaint is that the WLC fitting of the data is sometimes absolutely horrid,
(where the y axis is force in pN, and the x axis is extension in nm) and I’m wondering if this is just a case of good data being hard to come by, or the fact that the WLC model really isn’t applicable to protein unfolding. In the case of DNA, the model miserably fails at around 20-30 pN, while here the model is applied all the way up to (in some cases) 600 pN. Perhaps our local AFM expert can comment!