How Does a Hydrophobic Macromolecule Respond to a Mixed Osmolyte Environment?

Area of Science:

• Biophysical Chemistry
• Polymer Science
• Computational Chemistry

Background:

• Trimethyl N-oxide (TMAO) is known to protect proteins from urea's denaturing effects.
• The influence of osmolytes on hydrophobic interactions in polymer folding is debated.
• Individual TMAO and urea solutions affect hydrophobic polymer conformations differently.

Purpose of the Study:

• To investigate the conformational behavior of hydrophobic polymers in mixed aqueous solutions of TMAO and urea.
• To elucidate the mechanistic role of osmolytes in polymer folding and hydrophobic interactions.

Main Methods:

• Free energy based simulations were employed.
• Both a model hydrophobic polymer and polystyrene were simulated.
• Simulations were conducted in aqueous mixtures of TMAO and urea across various concentrations.

Main Results:

• Contrary to protein behavior, TMAO addition to urea solutions further destabilized the collapsed polymer conformation.
• Mixed osmolyte solutions exhibited a higher destabilization extent than pure urea solutions.
• Cosolutes preferentially bound to the extended polymer conformation, supporting preferential solvation theory.

Conclusions:

• The action of mixed osmolyte solutions on hydrophobic polymers is distinct from their effect on proteins.
• TMAO reinforces urea's destabilizing effect on hydrophobic polymers, contrasting its protective role in proteins.
• Findings highlight the complex interplay of osmolytes and polymer conformation.