Microscopic mechanism of protein cryopreservation in an aqueous solution with trehalose.

In order to investigate the cryoprotective mechanism of trehalose on proteins, we use molecular dynamics computer simulations to study the microscopic dynamics of water upon cooling in an aqueous solution of lysozyme and trehalose. We find that the presence of trehalose causes global retardation of the dynamics of water. Comparing aqueous solutions of lysozyme with/without trehalose, we observe that the dynamics of water in the hydration layers close to the protein is dramatically slower when trehalose is present in the system. We also analyze the structure of water and trehalose around the lysozyme and find that the trehalose molecules form a cage surrounding the protein that contains very slow water molecules. We conclude that the transient cage of trehalose molecules that entraps and slows the water molecules prevents the crystallisation of protein hydration water upon cooling.

Confinement of anomalous liquids in nanoporous matrices.

Using molecular dynamics simulations, we investigate the effects of different nanoconfinements on complex liquids-e.g., colloids or protein solutions-with density anomalies and a liquid-liquid phase transition (LLPT). In all the confinements, we find a strong depletion effect with a large increase in liquid density near the confining surface. If the nanoconfinement is modeled by an ordered matrix of nanoparticles, we find that the anomalies are preserved. On the contrary, if the confinement is modeled by a disordered matrix of nanoparticles, we find a drastically different phase diagram: the LLPT shifts to lower pressures and temperatures, and the anomalies become weaker, as the disorder increases. We find that the density heterogeneities induced by the disordered matrix are responsible for the weakening of the LLPT and the disappearance of the anomalies.

Effect of hydrophobic environments on the hypothesized liquid-liquid critical point of water.

The complex behavior of liquid water, along with its anomalies and their crucial role in the existence of life, continue to attract the attention of researchers. The anomalous behavior of water is more pronounced at subfreezing temperatures and numerous theoretical and experimental studies are directed towards developing a coherent thermodynamic and dynamic framework for understanding supercooled water. The existence of a liquid-liquid critical point in the deep supercooled region has been related to the anomalous behavior of water. However, the experimental study of supercooled water at very low temperatures is hampered by the homogeneous nucleation of the crystal. Recently, water confined in nanoscopic structures or in solutions has attracted interest because nucleation can be delayed. These systems have a tremendous relevance also for current biological advances; e.g., supercooled water is often confined in cell membranes and acts as a solvent for biological molecules. In particular, considerable attention has been recently devoted to understanding hydrophobic interactions or the behavior of water in the presence of apolar interfaces due to their fundamental role in self-assembly of micelles, membrane formation and protein folding. This article reviews and compares two very recent computational works aimed at elucidating the changes in the thermodynamic behavior in the supercooled region and the liquid-liquid critical point phenomenon for water in contact with hydrophobic environments. The results are also compared to previous reports for water in hydrophobic environments.

Large decrease of fluctuations for supercooled water in hydrophobic nanoconfinement.

Using Monte Carlo simulations, we study a coarse-grained model of a water layer confined in a fixed disordered matrix of hydrophobic nanoparticles at different particle concentrations c. For c=0, we find a first-order liquid-liquid phase transition (LLPT) ending in one critical point at low pressure P. For c>0, our simulations are consistent with a LLPT line ending in two critical points at low and high P. For c=25%, at high P and low temperature, we find a dramatic decrease of compressibility, thermal expansion coefficient, and specific heat. Surprisingly, the effect is present also for c as low as 2.4%. We conclude that even a small presence of hydrophobic nanoparticles can drastically suppress thermodynamic fluctuations, making the detection of the LLPT more difficult.