  Hypotheses: Additives are commonly used to tune macromolecular conformational
transitions. Among additives, trehalose is an excellent bioprotectant and among
responsive polymers, PNIPAM is the most studied material. Nevertheless, their
interaction mechanism so far has only been hinted without direct investigation,
and, crucially, never elucidated in comparison to proteins. Detailed insights
would help understand to what extent PNIPAM microgels can effectively be used
as synthetic biomimetic materials, to reproduce and study, at the colloidal
scale, isolated protein behavior and its sensitivity to interactions with
specific cosolvents or cosolutes. Experiments: The effect of trehalose on the
swelling behavior of PNIPAM microgels was monitored by dynamic light
scattering; Raman spectroscopy and molecular dynamics simulations were used to
explore changes of solvation and dynamics across the swelling-deswelling
transition at the molecular scale. Findings: Strongly hydrated trehalose
molecules develop water-mediated interactions with PNIPAM microgels, thereby
preserving polymer hydration below and above the transition while drastically
inhibiting local motions of the polymer and of its hydration shell. Our study,
for the first time, demonstrates that slowdown of dynamics and preferential
exclusion are the principal mechanisms governing trehalose effect on PNIPAM
microgels, at odds with preferential adsorption of alcohols, but in full
analogy with the behavior observed in trehalose-protein systems.
