The ability of trimethylamine N-oxide to resist pressure induced perturbations to water structure

Trimethylamine N-oxide (TMAO) protects organisms from the damaging effects of deep-sea high pressure, but it is not well understood how pressure and TMAO in combination perturb the water structure. Here, the authors use neutron scattering coupled with computational modelling of water at 25 bar and 4 kbar in the presence and absence of TMAO to propose an osmolyte protection ratio at which pressure and TMAO-induced energy changes effectively cancel out, which translates across scales to the organism level. Trimethylamine N-oxide (TMAO) protects organisms from the damaging effects of high pressure. At the molecular level both TMAO and pressure perturb water structure but it is not understood how they act in combination. Here, we use neutron scattering coupled with computational modelling to provide atomistic insight into the structure of water under pressure at 4 kbar in the presence and absence of TMAO. The data reveal that TMAO resists pressure-induced perturbation to water structure, particularly in retaining a clear second solvation shell, enhanced hydrogen bonding between water molecules and strong TMAO - water hydrogen bonds. We calculate an 'osmolyte protection' ratio at which pressure and TMAO-induced energy changes effectively cancel out. Remarkably this ratio translates across scales to the organism level, matching the observed concentration dependence of TMAO in the muscle tissue of organisms as a function of depth. Osmolyte protection may therefore offer a molecular mechanism for the macroscale survival of life in extreme environments.

Automated summary

Trimethylamine N-oxide (TMAO) protects organisms from high pressure damage. Both TMAO and pressure affect water structure at the molecular level, but their combined action is not well understood. In this study, neutron scattering and computational modeling were used to investigate the influence of TMAO on water structure under 4 kbar pressure. The results show that TMAO can counteract the pressure-induced perturbation of water structure, particularly in maintaining a clear second solvation shell, enhancing hydrogen bonding between water molecules, and forming strong TMAO-water hydrogen bonds. An 'osmolyte protection' ratio at which pressure and TMAO-induced energy changes cancel out was calculated. Remarkably, this ratio also matches the concentration dependence of TMAO in organism muscle tissue as a function of depth. Therefore, osmolyte protection may provide a molecular mechanism for the survival of life in extreme environments.