Identifying Chaotropic and Kosmotropic Agents by Nanorheology

Chemical agents are classified into chaotropes (disorder inducing) and kosmotropes (order inducing) based on their ability to destabilize or stabilize, respectively, the structure of hydrated macromolecules and their solutions. Here, we examine the effect of such agents on the mechanical stiffness of the hydration layer of proteins, measured by nanorheology. We examine four different agents and conclude that chaotropic substances induce the overall softening of the protein-hydration layer system, whereas the kosmotropic substances induce stiffening. Specifically, with glucose and trifluoroethanol, two known kosmotropic agents, we observe the stiffening of the hydration layer. In contrast, with guanidine hydrochloride and urea, known kaotropic agents, we observe softening. Thus, the viscoelastic mechanics of the folded, hydrated protein provides an experimental measure of the effect that chaotropes and kosmotropes have on the dynamics.