Guanidinium can both Cause and Prevent the Hydrophobic Collapse of Biomacromolecules

TL;DR

This study investigates how guanidinium salts influence the stability of elastin-like polypeptides, revealing that their effects depend on the specific counteranion and salt concentration, leading to both stabilization and destabilization of the collapsed state.

Contribution

It provides a detailed mechanistic understanding of how different guanidinium salts can both cause and prevent hydrophobic collapse in biomacromolecules, highlighting the role of ion pairing and concentration.

Findings

Guanidinium's effect depends on the counteranion and salt concentration.

Sulfate stabilizes the collapsed state via depletion effects.

SCN- stabilizes the collapsed state at low concentrations by crosslinking.

Abstract

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.