How osmolytes influence hydrophobic polymer conformations: A unified view from experiment and theory.

Jagannath Mondal , Duncan Halverson , Isaac T S Li , Guillaume Stirnemann (1, 2) , Gilbert C Walker , Bruce J Berne

1 PASTEUR - Processus d'Activation Sélective par Transfert d'Energie Uni-électronique ou Radiatif (UMR 8640)
2 Department of Chemistry [New York]

It is currently the consensus belief that protective osmolytes such as trimethylamine N-oxide (TMAO) favor protein folding by being excluded from the vicinity of a protein, whereas denaturing osmolytes such as urea lead to protein unfolding by strongly binding to the surface. Despite there being consensus on how TMAO and urea affect proteins as a whole, very little is known as to their effects on the individual mechanisms responsible for protein structure formation, especially hydrophobic association. In the present study, we use single-molecule atomic force microscopy and molecular dynamics simulations to investigate the effects of TMAO and urea on the unfolding of the hydrophobic homopolymer polystyrene. Incorporated with interfacial energy measurements, our results show that TMAO and urea act on polystyrene as a protectant and a denaturant, respectively, while complying with Tanford-Wyman preferential binding theory. We provide a molecular explanation suggesting that TMAO molecules have a greater thermodynamic binding affinity with the collapsed conformation of polystyrene than with the extended conformation, while the reverse is true for urea molecules. Results presented here from both experiment and simulation are in line with earlier predictions on a model Lennard-Jones polymer while also demonstrating the distinction in the mechanism of osmolyte action between protein and hydrophobic polymer. This marks, to our knowledge, the first experimental observation of TMAO-induced hydrophobic collapse in a ternary aqueous system.

Mots clés: Atomic Force; Computer Simulation; Hydrophobic and Hydrophilic Interactions; Mechanical; Methylamines; Methylamines: chemistry; Microscopy; Molecular Dynamics Simulation; Normal Distribution; Polymers; Polymers: chemistry; Polystyrenes; Polystyrenes: chemistry; Protein Binding; Protein Conformation; Protein Folding; Proteins; Proteins: chemistry; Software; Solvents; Solvents: chemistry; Stress; Thermodynamics; Urea; Urea: chemistry; Water; Water: chemistry

Domaines: Biophysique

Jagannath Mondal, Duncan Halverson, Isaac T S Li, Guillaume Stirnemann, Gilbert C Walker, et al.. How osmolytes influence hydrophobic polymer conformations: A unified view from experiment and theory.. Proceedings of the National Academy of Sciences of the United States of America, 2015, 112, pp.9270--5. ⟨10.1073/pnas.1511780112⟩. ⟨hal-01498018⟩