Advances over the past decade have made it possible to extract elastic constants of lipid assemblies from molecular dynamics simulations. We summarize existing strategies for obtaining membrane elastic moduli and clarify the differences in the underlying approaches. We analyze these strategies in depth, including several important advantages and limitations. By addressing these limitations, we obtain a newly formulated spatially local methodology for extracting bending and tilt moduli: The Real Space Instantaneous Surface Method (ReSIS). With its freely available implementation, this method is designed for highly dynamic systems with arbitrary interface geometries. We demonstrate how the method provides consistent results for membranes of arbitrary size. In addition, we describe alternative implementations of various Fourier-space methods, and use these to compare the results from the different available methods and from published computational data. We specifically focus on the tilt modulus, where very large differences between Fourier and real-space based methods are observed, including those derived using ReSIS. These discrepancies are likely due to the known difference between model moduli and thermodynamic moduli that are derived from the corresponding response functions. In addition, we reexamine the issue of angular degeneracy and its effect on conformational ensembles. Finally, a van ’t Hoff analysis of the tilt and bending moduli reveals that both modes act as entropic springs and that enthalpy favors nonzero tilt, perhaps heralding the spontaneous lipid chain tilt of the gel phase at lower temperatures.
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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 concentraion 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.
Under environmental duress, many organisms accumulate large amounts of osmolytes – molecularly small organic solutes. Osmolytes are known to counteract stress, driving proteins to their compact native states by their exclusion from protein surfaces. In contrast, the effect of osmolytes on lipid membranes is poorly understood and widely debated. Many fully membrane-permeable osmolytes exert an apparent attractive force between lipid membranes, yet all proposed models fail to fully account for the origin of this force. We follow the quintessential osmolyte trimethylamine N-oxide (TMAO) and its interaction with dimyristoyl phosphatidylcholine (DMPC) membranes in aqueous solution. We find that by partitioning away from the inter-bilayer space, TMAO pushes adjacent membranes closer together. Experiments and simulations further show that the partitioning of TMAO away from the volume between bilayers stems from its exclusion from the lipid–water interface, similar to the mechanism of protein stabilization by osmolytes. We extend our analysis to show that the preferential interaction of other physiologically relevant solutes (including sugars and DMSO) also correlates with their effect on membrane bilayer interactions. Our study resolves a long-standing puzzle, explaining how osmolytes can increase membrane– membrane attraction or repulsion depending on their preferential interactions with lipids.