  A combination of Fourier transform infrared and phase transition measurements
as well as molecular computer simulations, and thermodynamic modeling were
performed to probe the mechanisms by which guanidinium salts influence the
stability of the collapsed versus uncollapsed state of an elastin-like
polypeptide (ELP), an uncharged thermoresponsive polymer. We found that the
cation's action was highly dependent upon the counteranion with which it was
paired. Specifically, Gnd+ was depleted from the ELP/water interface and was
found to stabilize the collapsed state of the macromolecule when paired with
well-hydrated anions such as sulfate. Stabilization in this case occurred via
an excluded volume (or depletion) effect, whereby sulfate was strongly
partitioned away from the ELP/water interface. Intriguingly, at low salt
concentrations, Gnd+ was also found to stabilize the collapsed state of the ELP
when paired with SCN-, which is a strong binder for the ELP. In this case, the
anion and cation were both found to be enriched in the collapsed state of the
polymer. The collapsed state was favored because the Gnd+ crosslinked the
polymer chains together. Moreover, the anion helped partition Gnd+ to the
polymer surface. At higher salt concentrations (>1.5 M), GndSCN switched to
stabilizing the uncollapsed state because a sufficient amount of Gnd+ and SCN-
partitioned to the polymer surface to prevent cross-linking from occurring.
Finally, in a third case, it was found that salts which interacted in an
intermediate fashion with the polymer (e.g. GndCl) favored the uncollapsed
conformation at all salt concentrations.
