We present a mechanism for a generic, powerful force of assembly and mobility for transmembrane proteins in lipid bilayers. This force is a pre-transition (or pre-melting) effect for the first-order transition between ordered and disordered phases in the membrane. Using large-scale molecular simulation, we show that a protein with hydrophobic thickness equal to that of the disordered phase embedded in an ordered bilayer stabilizes a microscopic order–disorder interface. The stiffness of that interface is finite. When two such proteins approach each other, they assemble because assembly reduces the net interfacial energy. Analogous to the hydrophobic effect, we refer to this phenomenon as the 'orderphobic effect'. The effect is mediated by proximity to the order–disorder phase transition and the size and hydrophobic mismatch of the protein. The strength and range of forces arising from this effect are significantly larger than those that could arise from membrane elasticity for the membranes considered.DOI: http://dx.doi.org/10.7554/eLife.13150.001

Abstract. Glass transitions from liquid to semi-solid and solid phase states have important implications for reactivity, growth, and cloud-forming (cloud condensation nuclei and ice nucleation) capabilities of secondary organic aerosols (SOAs). The small size and relatively low mass concentration of SOAs in the atmosphere make it difficult to measure atmospheric SOA glass transitions using conventional methods. To circumvent these difficulties, we have adapted a new technique for measuring glass-forming properties of atmospherically relevant organic aerosols. Aerosol particles to be studied are deposited in the form of a thin film onto an interdigitated electrode (IDE) using electrostatic precipitation. Dielectric spectroscopy provides dipole relaxation rates for organic aerosols as a function of temperature (373 to 233 K) that are used to calculate the glass transition temperatures for several cooling or heating rates. IDE-enabled broadband dielectric spectroscopy (BDS) was successfully used to measure the kinetically controlled glass transition temperatures of aerosols consisting of glycerol and four other compounds with selected cooling and heating rates. The glass transition results agree well with available literature data for these five compounds. The results indicate that the IDE-BDS method can provide accurate glass transition data for organic aerosols under atmospheric conditions. The BDS data obtained with the IDE-BDS technique can be used to characterize glass transitions for both simulated and ambient organic aerosols and to model their climate effects.

We present a model for glassy dynamics in supercooled liquid mixtures. Given the relaxation behavior of individual supercooled liquids, the model predicts the relaxation times of their mixtures as temperature is decreased. The model is based on dynamical facilitation theory for glassy dynamics, which provides a physical basis for relaxation and vitrification of a supercooled liquid. This is in contrast to empirical linear interpolations such as the Gordon-Taylor equation typically used to predict glass transition temperatures of liquid mixtures. To understand the behavior of supercooled liquid mixtures we consider a multi-component variant of the kinetically constrained East model in which components have a different energy scale and can also diffuse when locally mobile regions, i.e., excitations, are present. Using a variational approach we determine an effective single component model with a single effective energy scale that best approximates a mixture. When scaled by this single effective energy, we show that experimental relaxation times of many liquid mixtures all collapse onto the 'parabolic law' predicted by dynamical facilitation theory. The model can be used to predict transport properties and glass transition temperatures of mixtures of glassy materials, with implications in atmospheric chemistry, biology, and pharmaceuticals.This paper presents a model for glassy dynamics in mixtures of liquids. Understanding and predicting glassy behavior of liquid mixtures and solutions has been important in investigating the fundamental properties of glassy dynamics and the glass transition [1-3], as well as in areas of research where solutions of liquids undergo vitrification into amorphous solids, and where crystallization needs to be avoided. These areas include chemistry of solutions [4], and pharmaceutical and food industries [5][6][7]. Insight into properties of glassy mixtures is also important in more complex systems such as atmospheric organic aerosols that show glassy behaviour [8][9][10][11], and in the preservation of biological cells where vitrification may assist the recovery of cells after freezing and/or desiccation [12,13]. The typical approach to predict the glass transition temperature of liquid mixtures is an empirical linear interpolation between the glass transition temperatures of individual components, such as the Gordon-Taylor equation [14], without a physical basis in a microscopic theory for glassy dynamics. In this work we use the perspective of dynamical facilitation theory to develop a model for glassy dynamics of binary mixtures, which can be used to predict relaxation behavior and glass transition temperatures of supercooled liquid mixtures.When a glass-former is cooled below its onset temperature (T o ) its relaxation time exhibits a super-Arrhenius increase with decreasing temperature [15,16], and its microstructure exhibits dynamical heterogeneity, i.e., transient but distinct mesoscopic regions of particle mobility and immobility. The increase in relaxation time is explained by d...

We demonstrate pretransition effects in space-time in trajectories of systems in which the dynamics displays a first-order phase transition between distinct dynamical phases. These effects are analogous to those observed for thermodynamic first-order phase transitions, most notably the hydrophobic effect in water. Considering the (infinite temperature) East model as an elementary example, we study the properties of "space-time solvation" by examining trajectories where finite space-time regions are conditioned to be inactive in an otherwise active phase. We find that solvating an inactive region of space-time within an active trajectory shows two regimes in the dynamical equivalent of solvation free energy: an "entropic" small solute regime in which uncorrelated fluctuations are sufficient to evacuate activity from the solute, and an "energetic" large solute regime which involves the formation of a solute-induced inactive domain with an associated active-inactive interface bearing a dynamical interfacial tension. We also show that as a result of this dynamical interfacial tension there is a dynamical analog of the hydrophobic collapse that drives the assembly of large hydrophobes in water. We discuss the general relevance of these results to the properties of dynamical fluctuations in systems with slow collective relaxation such as glass formers.

Phospholipid flip-flop in the endoplasmic reticulum (ER) is very rapid and non-specific to phospholipid headgroups, which is necessary to maintain lipid homeostasis in the membrane. Much research suggested that the rapid flip-flop in the ER is mediated by membrane proteins. However, ''flippases'', which are responsible for the flip-flop, have not been identified yet. We have previously demonstrated that peptide sequences that contain a hydrophilic residue in the transmembrane region are effective to promote the flipflop and that such sequences can be seen in the transmembrane region of ER proteins predicted by SOSUI. Therefore, we hypothesized that ER proteins with hydrophilic residues in the transmembrane region may promote the flip-flop. In this study, we synthesized peptides with membranespanning sequences of several ER proteins and investigated their flip-flop promotion abilities by using fluorescent-labeled phospholipids. We found that the sequences of EDEM1 and SPAST promoted the flip-flop of fluorescent lipids non-selectively with respect to the glycerophospholipid structure. These two peptides contain both positively charged Arg and noncharged His near the center of the sequences. Thus, we next examined how the flip-flop promotion abilities were altered by substitution of hydrophobic Ala for Arg or His. The Arg to Ala mutation inhibited the flip-flop promotion abilities of each peptides completely, while the His to Ala mutation did partly. These results suggested that both Arg and His are responsible for the flip-flop promotion by the peptides and Arg plays a vital role in the activities. Considering the high activity of the EDEM1 peptide observed at significantly low peptide concentrations, EDEM1 protein might act as a ''flippase''.