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Dramatic increase in NaCl consumption lead to sodium intake beyond health guidelines. KCl substitution helps reduce sodium intake but results in a bitter-metallic off-taste. Two disaccharides, trehalose and sucrose, were tested in order to untangle the chemical (increase in effective concentration of KCl due to sugar addition) from the sensory effects. The bitter-metallic taste of KCl was reduced by these sugars, while saltiness was enhanced or unaltered. The perceived sweetness of sugar, regardless of its type and concentration, was an important factor in KCl taste modulation. Though KCl was previously shown to increase the chemical activity of trehalose but not of sucrose, we found that it suppressed the perceived sweetness of both sugars. Therefore, sensory integration was the dominant factor in the tested KCl-sugar combinations. [ABSTRACT FROM AUTHOR]

From colloidal dispersions to solvated polymers or proteins, solution composition is known to strongly influence the stable state of the bathing macromolecules. Mixed solvents containing species with different affinities to specific macromolecular states can shift equilibrium towards the thermodynamically preferred state with lower free energy, even when the molecular interactions with the solvent are weak. We review two known mechanisms, bridging and depletion attraction, and discuss how each can emerge, depending on the molecular size and interaction of the mixed solvent species. We show that simple theoretical considerations predict that the macromolecular state that is stabilized by each mechanism possesses unique structural properties, as well as distinct thermodynamic fingerprints. Furthermore, we demonstrate the mechanistic role of enthalpy and entropy, as seen in a simple mean field model of macromolecules in mixed solvents. These thermodynamic contributions determine the temperature dependence of cosolute induced effects. Finally, we review the possible role of fluctuations, and point to possible implications and open questions. [ABSTRACT FROM AUTHOR]

Cosolutes excluded from macromolecules create effective attractions between the excluding macromolecules, and promote their self-association. This “depletion force” serves an important stabilizing role in many biological and technological processes. Specifically, many osmolytes and polymeric crowders that are excluded from protein surfaces stabilize the more compact folded state. Yet, these excluded cosolutes operate through several, thermodynamically distinct, mechanisms. Here we review the experimentally found mechanisms and link these to possible underlying molecular interactions. One class of excluded cosolutes comprises protective osmolytes. These tend to induce attractive depletion forces that are enthalpically dominated but entropically destabilizing. Whereas polymeric crowders may act by similar mechanisms to osmolytes, in many other cases they induce depletion forces dominated by favorable entropy. These different thermodynamic mechanisms are intimately related to the effective interaction of cosolute with each macromolecule. The venerable Asakura-Oosawa model for depletion forces assumes that the cosolute-macromolecule interaction is entirely steric, thereby predicting fully entropic depletion forces. Augmenting this steric repulsion core with a “soft” repulsion shell adds an enthalpic contribution to the depletion force, which may even dominate all other contributions. Further, considering that cosolute-macromolecule effective interactions are temperature-dependent results in a depletion force that can be concertedly dominated by enthalpy and entropically disfavored, as observed experimentally for protective osmolytes. In this core-shell description, to account for depletion forces that are enthalpically dominated and entropically disfavored, it is sufficient to consider an effective microscopic cosolute-macromolecule soft shell that comprises an entropic attraction and an enthalpic repulsion. We show how the full gamut of cosolute effects can be rationalized using these simple considerations regarding the nature of the cosolute-macromolecule effective interaction. [ABSTRACT FROM AUTHOR]

Abstract: Serving as a crucial component of mammalian cells, cholesterol critically regulates the functions of biomembranes. This review focuses on a specific property of cholesterol and other sterols: the tilt modulus χ that quantifies the energetic cost of tilting sterol molecules inside the lipid membrane. We show how χ is involved in determining properties of cholesterol-containing membranes, and detail a novel approach to quantify its value from atomistic molecular dynamics (MD) simulations. Specifically, we link χ with other structural, thermodynamic, and mechanical properties of cholesterol-containing lipid membranes, and delineate how this useful parameter can be obtained from the sterol tilt probability distributions derived from relatively small-scale unbiased MD simulations. We demonstrate how the tilt modulus quantitatively describes the aligning field that sterol molecules create inside the phospholipid bilayers, and we relate χ to the bending rigidity of the lipid bilayer through effective tilt and splay energy contributions to the elastic deformations. Moreover, we show how χ can conveniently characterize the “condensing effect” of cholesterol on phospholipids. Finally, we demonstrate the importance of this cholesterol aligning field to the proper folding and interactions of membrane peptides. Given the relative ease of obtaining the tilt modulus from atomistic simulations, we propose that χ can be routinely used to characterize the mechanical properties of sterol/lipid bilayers, and can also serve as a required fitting parameter in multi-scaled simulations of lipid membrane models to relate the different levels of coarse-grained details. [Copyright &y& Elsevier]

Trehalose is revered for its multiple unique impacts on solution properties, including the ability to modulate the salty and bitter tastes of sodium and potassium salts. However, the molecular mechanisms underlying trehalose’s effect on taste perception are unknown. Here we focus on the physico-chemical effect of trehalose to alter the activity of monovalent salts in aqueous solution. Using a modified isopiestic methodology that relies on contemporary vapor pressure osmometry, we elucidate how trehalose modifies the thermodynamic chemical activity of sodium and potassium chloride, as well as the effect of the salts on the sugar's activity. We find that trehalose has a specific impact on potassium chloride that is unlike that of other sugars or polyols. Remarkably, especially at low salt concentrations, trehalose considerably elevates the activity (or chemical potential) of KCl, raising the salt activity coefficient as high as ∼1.5 its value in the absence of the sugar. Moreover, in contrast to their action on other known carbohydrates, both KCl and NaCl act as salting-out agents towards trehalose, as seen in the elevated activity coefficient compared with its value in pure water (up to ∼1.5 higher at low sugar and salt concentrations). We discuss the possible relevance of our findings to the mechanism of trehalose taste perception modification, and point to necessary future directed sensory experiments needed to resolve the possible link between our findings and the emerging biochemical or physiological mechanisms involved. [ABSTRACT FROM AUTHOR]

Abstract: Solutes added to solutions often dramatically impact molecular processes ranging from the suspension or precipitation of colloids to biomolecular associations and protein folding. Here we revisit the origins of the effective attractive interactions that emerge between and within macromolecules immersed in solutions containing cosolutes that are preferentially excluded from the macromolecular interfaces. Until recently, these depletion forces were considered to be entropic in nature, resulting primarily from the tendency to increase the space available to the cosolute. However, recent experimental evidence indicates the existence of additional, energetically-dominated mechanisms. In this review we follow the emerging characteristics of these different mechanisms. By compiling a set of available thermodynamic data for processes ranging from protein folding to protein–protein interactions, we show that excluded cosolutes can act through two distinct mechanisms that correlate to a large extent with their molecular properties. For many polymers at low to moderate concentrations the steric interactions and molecular crowding effects dominate, and the mechanism is entropic. To contrast, for many small excluded solutes, such as naturally occurring osmolytes, the mechanism is dominated by favorable enthalpy, whereas the entropic contribution is typically unfavorable. We review the available models for these thermodynamic mechanisms, and comment on the need for new models that would be able to explain the full range of observed depletion forces. [Copyright &y& Elsevier]

The behavior of oxysterols in phospholipid membranes and their effects on membrane properties were investigated by means of dynamic light scattering, fluorescence spectroscopy, NMR, and extensive atomistic simulations. Two families of oxysterols were scrutinized—tail-oxidized sterols, which are mostly produced by enzymatic processes, and ring-oxidized sterols, formed mostly via reactions with free radicals. The former family of sterols was found to behave similar to cholesterol in terms of molecular orientation, roughly parallel to the bilayer normal, leading to increasing membrane stiffness and suppression of its membrane permeability. In contrast, ring-oxidized sterols behave quantitatively differently from cholesterol. They acquire tilted orientations and therefore disrupt the bilayer structure with potential implications for signaling and other biochemical processes in the membranes. [ABSTRACT FROM AUTHOR]

Abstract: In aqueous solutions, dissolved ions interact strongly with the surrounding water and surfaces, thereby modifying solution properties in an ion-specific manner. These ion-hydration interactions can be accounted for theoretically on a mean-field level by including phenomenological terms in the free energy that correspond to the most dominant ion-specific interactions. Minimizing this free energy leads to modified Poisson-Boltzmann equations with appropriate boundary conditions. Here, we review how this strategy has been used to predict some of the ways ion-specific effects can modify the forces acting within and between charged interfaces immersed in salt solutions. [Copyright &y& Elsevier]