Brownian motion of single glycerol molecules in an aqueous solution as studied by dynamic light scattering

Aqueous solutions of glycerol are investigated by dynamic light scattering (DLS) over the whole concentration range (10-98 wt.% water) and in the temperature range 283-303 K. The measurements reveal one slow relaxation process in the geometry of polarized light scattering. This process is present in the whole concentration range, although it is very weak at the highest and lowest water concentrations and is considerably slower than the structural alpha relaxation, which is too fast to be observed on the experimental time scale in the measured temperature range. The relaxation time of the observed process exhibits a 1/q(2) dependence, proving that it is due to long-range translational diffusion. The Stokes-Einstein relation is used to estimate the hydrodynamic radius of the diffusing particles and from these calculations it is evident that the observed relaxation process is due to the Brownian motion of single or a few glycerol molecules. The fact that it is possible to study the self-diffusion of such small molecules may stimulate a broadening of the research field used to be covered by the DLS technique

The glass transition and relaxation behavior of bulk water and a possible relation to confined water

Due to the widespread importance of water and the difficulty to study it in the so-called no man's land between 150 and 235 K, deeply supercooled bulk water is currently heavily debated. It speculates about its properties from extrapolations of experimental data on bulk water above 235 K and below 150 K, computer simulations, and experiments on confined water for which the finite size effects may prevent crystallization in the no man's land. However, it is far from obvious how experimental data on bulk water should be extrapolated to the temperature range of the no man's land or how relevant results from computer simulations and studies of confined water are for bulk water. In this paper the structural and dynamical properties of supercooled bulk water are tried to be understood from experimental results on confined water and comparisons with bulk water. We propose that a similar crossover from a high temperature alpha-relaxation to a low temperature beta-relaxation occurs also for bulk water but at a higher temperature than for confined water due to the larger average number of hydrogen bonds between the water molecules in bulk water. In the case of bulk water the crossover is expected to occur around the critical temperature T-s approximate to 228 K when the buildup of an icelike tetrahedral network structure is completed. The proposed interpretation is the simplest one that is able to explain many of the peculiar properties of supercooled water

The slow dielectric Debye relaxation of monoalcohols in confined geometries

Broadband dielectric relaxation measurements have been performed on monoalcohols confined in the quasi-two-dimensional space between clay platelets and the quasi-one-dimensional pores of approximately 10 angstrom diameter in a molecular sieve. Interestingly, the results show that the slow Debye-like process is present even in these severe confinements, proving that structural models that are based on two-dimensional or three-dimensional cluster formations as the structural origin of the Debye-like process can be excluded. Rather, the insensitivity of its time-scale to confinements suggests that it is of local character and in some way related to the lifetime or breaking and reformation of hydrogen bonds. (C) 2011 American Institute of Physics. [doi:10.1063/1.3563630

The protein glass transition as measured by dielectric spectroscopy and differential scanning calorimetry

The glass transition and its related dynamics of myroglobin in water and in a water-glycerol mixture have been investigated by dielectric spectroscopy and differential scanning calorimetry (DSC). For all samples, the DSC measurements display a glass transition that extends over a large temperature range. Both the temperature of the transition and its broadness decrease rapidly with increasing amount of solvent in the system. The dielectric measurements show several dynamical processes, due to both protein and solvent relaxations, and in the case of pure water as solvent the main protein process (which most likely is due to conformational changes of the protein structure) exhibits a dynamic glass transition (i.e. reaches a relaxation time of 100 s) at about the same temperature as the calorimetric glass transition temperature Tg is found. This glass transition is most likely caused by the dynamic crossover and the associated vanishing of the alpha-relaxation of the main water relaxation, although it does not contribute to the calorimetric Tg. This is in contrast to myoglobin in water-glycerol, where the main solvent relaxation makes the strongest contribution to the calorimetric glass transition. For all samples it is clear that several proteins processes are involved in the calorimetric glass transition and the broadness of the transition depends on how much these different relaxations are separated in time

DOPC versus DOPE as a helper lipid for gene-therapies: molecular dynamics simulations with DLin-MC3-DMA

Ionizable lipids are important compounds of modern therapeutic lipid nano-particles (LNPs). One of the most promising ionizable lipids (or amine lipids) is DLin-MC3-DMA. Depending on their pharmaceutical application these LNPs can also contain various helper lipids, such as phospho- and pegylated lipids, cholesterol and nucleic acids as a cargo. Due to their complex compositions the structures of these therapeutics have not been refined properly. Therefore, the role of each lipid in the pharmacological properties of LNPs has not been determined. In this work an atomistic model for the neutral form of DLin-MC3-DMA was derived and all-atom molecular dynamics (MD) simulations were carried out in order to investigate the effect of the phospholipid headgroup on the possible properties of the shell-membranes of LNPs. Bilayers containing either DOPC or DOPE lipids at two different ratios of DLin-MC3-DMA (5 mol% and 15 mol%) were constructed and simulated at neutral pH 7.4. The results from the analysis of MD trajectories revealed that DOPE lipid headgroups associated strongly with lipid tails and carbonyl oxygens of DLin-MC3-DMA, while for DOPC lipid headgroups no significant associations were observed. Furthermore, the strong associations between DOPE and DLin-MC3-DMA result in the positioning of DLin-MC3-DMA at the surface of the membrane. Such an interplay between the lipids slows down the lateral diffusion of all simulated bilayers, where a more dramatic decrease of the diffusion rate is observed in membranes with DOPE. This can explain the low water penetration of lipid bilayers with phosphatidylethanolamines and, probably, can relate to the bad transfection properties of LNPs with DOPE and DLin-MC3-DMA

Structural Comparison between Sucrose and Trehalose in Aqueous Solution

The two sugar molecules sucrose and trehalose are both considered as stabilizing molecules for the purpose of preserving biological materials during, for example, lyophilization or cryo-preservation. Although these molecules share a similar molecular structure, there are several important differences in their properties when they interact with water, such as differences in solubility, viscosity, and glass transition temperature. In general, trehalose has been shown to be more efficient than other sugar molecules in preserving different biological molecules against stress, and thus by investigating how these two disaccharides differ in their water interaction, it is possible to further understand what makes trehalose special in its stabilizing properties. For this purpose, the structure of aqueous solutions of these disaccharides was studied by using neutron and X-ray diffraction in combination with empirical potential structure refinement (EPSR) modeling. The results show that there are surprisingly few differences in the overall structure of the solutions, although there are indications for that trehalose perturbs the water structure slightly more than sucrose

Ionizable lipids penetrate phospholipid bilayers with high phase transition temperatures: perspectives from free energy calculations

The efficacies of modern gene-therapies strongly depend on their contents. At the same time the most potent formulations might not contain the best compounds. In this work we investigated the effect of phospholipids and their saturation on the binding ability of (6Z,9Z,28Z,31Z)-heptatriacont-6,9,28,31-tetraene-19-yl 4-(dimethylamino) butanoate (DLin-MC3-DMA) to model membranes at the neutral pH. We discovered that DLin-MC3-DMA has affinity to the most saturated monocomponent lipid bilayer 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) and an aversion to the unsaturated one 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC). The preference to a certain membrane was also well-correlated to the phase transition temperatures of phospholipid bilayers, and to their structural and dynamical properties. Additionally, in the case of the presence of DLin-MC3-DMA in the membrane with DOPC the ionizable lipid penetrated it, which indicates possible synergistic effects. Comparisons with other ionizable lipids were performed using a model lipid bilayer of 1-palmitoyl-2-oleoyl-glycero-3-phosphocholine (POPC). Particularly, the lipids heptadecan-9-yl 8-[2-hydroxyethyl-(6-oxo-6-undecoxyhexyl)amino]octanoate (SM-102) and [(4-hydroxybutyl) azanediyl] di(hexane-6,1-diyl) bis(2-hexyldecanoate) (ALC-0315) from modern mRNA-vaccines against COVID-19 were investigated and force fields parameters were derived for those new lipids. It was discovered that ALC-0315 binds strongest to the membrane, while DLin-MC3-DMA is not able to reside in the bilayer center. The ability to penetrate the membrane POPC by SM-102 and ALC-0315 can be related to their saturation, comparing to DLin-MC3-DMA

Role of Solvent for the Dynamics and the Glass Transition of Proteins

For the first time, a systematic investigation of the glass transition and its related dynamics of myoglobin in water-glycerol solvent mixtures of different water contents is presented. By a combination of broadband dielectric spectroscopy and differential scanning calorimetry (DSC), we have studied the relation between the protein and solvent dynamics with the aim to better understand the calorimetric glass transition, T-g, of proteins and the role of solvent for protein dynamics. The results show that both the viscosity related alpha-relaxation in the solvent as well as several different protein relaxations are involved in the calorimetric glass transition, and that the broadness (Delta T-g) of the transition depends strongly on the total amount of solvent. The main reason for this seems to be that the protein relaxation processes become more separated in time with decreasing solvent level. The results are compared to that of hydrated myoglobin where the hydration water does not give any direct contribution to the calorimetric T-g. However, the large-scale a-like relaxation in the hydration water is still responsible for the protein dynamics that freeze-in at T-g. Finally, the dielectric data show clearly that the protein relaxation processes exhibit similar temperature dependences as the alpha-relaxation in the solvent, as suggested for solvent-slaved protein motions

Interplay between Hydration Water and Headgroup Dynamics in Lipid Bilayers

In this study, the interplay between water and lipid dynamics has been investigated by broadband dielectric spectroscopy and modulated differential scanning calorimetry (MDSC). The rnultilamellar lipid bilayer system 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) has been studied over a broad temperature range at three different water contents: about 3, 6, and 9 water molecules per lipid molecule. The results from the dielectric relaxation measurements show that at temperatures <250 K the lipid headgroup rotation is described by a super-Arrhenius temperature dependence at the lowest hydration level and by the Arrhenius law at the highest hydration level. This difference in the temperature dependence of the lipid headgroup rotation can be explained by the increasing interaction between the headgroups with decreasing water content, which causes their rotational motion to be more cooperative in character. The main water relaxation shows an anomalous dependence on the water content in the supercooled and glassy regime. In contrast to the general behavior of interfacial water, the water dynamics is fastest in the driest sample and its temperature dependence is best described by a super-Arrhenius temperature dependence. The best explanation for this anomalous behavior is that the water relaxation becomes more determined by fast local lipid motions than by the intrinsic water dynamics at low water contents. In support for this interpretation is the finding that the relaxation time of the main water process is faster than that in most other host systems at temperatures below 180 K Thus, the dielectric relaxation data show clearly the strong interplay between water and lipid dynamics; the water influences the lipid dynamics and vice versa. In the MDSC data, we observe a weak enthalpy relaxation at 203 K for the driest sample and at 179 K for the most hydrated sample, attributed to the freezing-in of the lipid headgroup rotation observed in the dielectric data, since this motion reaches a time scale of about 100 s at about the same temperatures

Slow Debye-type peak observed in the dielectric response of polyalcohols

Dielectric relaxation spectroscopy of glass forming liquids normally exhibits a relaxation scenario that seems to be surprisingly general. However, the relaxation dynamics is more complicated for hydrogen bonded liquids. For instance, the dielectric response of monoalcohols is dominated by a mysterious Debye-like process at lower frequencies than the structural alpha-relaxation that is normally dominating the spectra of glass formers. For polyalcohols this process has been thought to be absent or possibly obscured by a strong contribution from conductivity and polarization effects at low frequencies. We here show that the Debye-like process, although much less prominent, is also present in the response of polyalcohols. It can be observed in the derivative of the real part of the susceptibility or directly in the imaginary part if the conductivity contribution is reduced by covering the upper electrode with a thin Teflon layer. We report on results from broadband dielectric spectroscopy studies of several polyalcohols: glycerol, xylitol, and sorbitol. The findings are discussed in relation to other experimental observations of ultraslow (i.e., slower than the viscosity related alpha-relaxation) dynamics in glass formers