Mechanisms for destabilisation of RNA viruses at air-water and liquid-liquid interfaces.

Understanding the interactions between viruses and surfaces or interfaces is important, as they provide the principles underpinning the cleaning and disinfection of contaminated surfaces. Yet, the physics of such interactions is currently poorly understood. For instance, there are longstanding experimental observations suggesting that the presence of air-water interfaces can generically inactivate and kill viruses, yet the mechanism underlying this phenomenon remains unknown. Here we use theory and simulations to show that electrostatics may provide one such mechanism, and that this is very general. Thus, we predict that the electrostatic free energy of an RNA virus should increase by several thousands of kBT as the virion breaches an air-water interface. We also show that the fate of a virus approaching a generic liquid-liquid interface depends strongly on the detailed balance between interfacial and electrostatic forces, which can be tuned, for instance, by choosing different media to contact a virus-laden respiratory droplet. Tunability arises because both the electrostatic and interfacial forces scale similarly with viral size. We propose that these results can be used to design effective strategies for surface disinfection.

Candidate gene studies in hypodontia suggest role for FGF3.

INTRODUCTION: The majority of tooth agenesis cases are mild (hypodontia) and typically not associated with the gene mutations linked to oligodontia. From this, we hypothesise that most cases of tooth agenesis fit a polygenic mode of inheritance, where several genes with small effects cause a variety of varying phenotypes. MATERIALS AND METHODS: In this study, we looked at 18 not typically studied genes in this condition, to ascertain their contribution to hypodontia. Our study subjects consisted of 167 patients with hypodontia and their parents from two cohorts (one from Brazil and one from Turkey). An additional 465 DNA samples (93 cases with hypodontia and 372 controls without family history for tooth agenesis or oral clefts) from Brazil were also available for this study. Ninety-three single nucleotide polymorphisms that maximally represent the linkage disequilibrium structure of the genes for the 18 genes were selected and genotyped using Taqman chemistry. Chi square was used to test if genotype distributions were in Hardy-Weinberg equilibrium, and 24 markers that were in Hardy-Weinberg equilibrium and had allele frequencies higher than 5 % in a panel of 50 CEPH samples were further tested. Association between hypodontia and genetic variants was tested with the transmission disequilibrium test within the programme Family-Based Association Test (FBAT) and by using Chi square and Fisher's exact tests. Alpha at a level of 0.05 was used to report results. RESULTS: Results suggest possible associations between several genes and hypodontia in the three populations. In the Turkish cohort (n = 51 parent-affected child trios) the most significant results were as follows: FGF3 rs1893047, p = 0.08; GLI3 rs929387, p = 0.03; GLI3 haplotype rs929387-rs846266, p = 0.002; and PAX9 rs2073242, p = 0.03. In the Brazilian cohort (n = 116 parent-affected child trios), the results were as follows: DLX1 rs788173, p = 0.07; FGF3 rs12574452, p = 0.03; GLI2 rs1992901, p = 0.03; and PITX2 rs2595110, p = 0.01. The second Brazilian cohort also suggested that FGF3 (rs12574452, p = 0.01) is associated with hypodontia and added EDAR (rs17269487, p = 0.04), LHX6 (rs989798, p = 0.02), and MSX1 (rs12532, p = 0.003). CONCLUSION: Our results suggest that several genes are potentially associated with hypodontia and their individual contributions may be modest. Hence, these cases may not be explained by inactivating mutations such as many oligodontia cases segregating in a Mendelian fashion but rather are influenced by one or more susceptibility alleles in multiple small effect genes.

Fine-mapping of 5q12.1-13.3 unveils new genetic contributors to caries.

Caries is a multifactorial disease and little is still known about the host genetic factors influencing susceptibility. Our previous genome-wide linkage scan has identified the interval 5q12.1-5q13.3 as linked to low caries susceptibility in Filipino families. Here we fine-mapped this region in order to identify genetic contributors to caries susceptibility. Four hundred and seventy-seven subjects from 72 pedigrees with similar cultural and behavioral habits and limited access to dental care living in the Philippines were studied. DMFT scores and genotype data of 75 single-nucleotide polymorphisms were evaluated in the Filipino families with the Family-Based Association Test. For replication purposes, a total 1,467 independent subjects from five different populations were analyzed in a case-control format. In the Filipino cohort, statistically significant and borderline associations were found between low caries experience and four genes spanning 13 million base pairs (PART1, ZSWIM6, CCNB1, and BTF3). We were able to replicate these results in some of the populations studied. We detected PART1 and BTF3 expression in whole saliva, and the expression of BTF3 was associated with caries experience. Our results suggest BTF3 may have a functional role in protecting against caries.

Tooth agenesis association with self-reported family history of cancer.

It has been proposed that tooth agenesis and cancer development share common molecular pathways. We performed a cross-sectional study to investigate the epidemiological and molecular association between tooth agenesis and self-reported family history of cancer. Eighty-two individuals with tooth agenesis and 328 individuals with no birth defect were recruited from the same institution. Tooth agenesis was assessed in permanent teeth and was defined based on the age of the participants and when initial tooth formation should be radiographically visible. We also investigated the role of genes involved in dental development that have been implicated in tumorigenesis, and 14 markers in AXIN2, FGF3, FGF10, and FGFR2 were genotyped. Individuals with tooth agenesis had an increased risk of having a family history of cancer (p = 0.00006; OR = 2.7; 95% C.I., 1.6-4.4). There were associations between AXIN2, FGF3, FGF10, and FGFR2 with tooth agenesis [i.e., individuals who carried the polymorphic allele of FGFR2 (rs1219648) presented higher risk for having premolar agenesis (p = 0.02; OR = 1.8; 95% C.I., 1.1-3.0)]. In conclusion, tooth agenesis was associated with positive self-reported family history of cancer and with variants in AXIN2, FGF3, FGF10, and FGFR2. Prospective studies are needed to confirm if tooth agenesis can be used as a risk marker for cancer.

Jamming in sheared foams and emulsions, explained by critical instability of the films between neighboring bubbles and drops.

Foam and emulsion jamming at low shear rates is explained by considering the thinning dynamics of the transient films, formed between neighboring bubbles and drops. After thinning gradually to a critical thickness, these films undergo an instability transition, which leads to the formation of very thin "black films" providing strong adhesion between the dispersed particles. Analysis shows that such film thickness instability occurs only if the contact time between particles is sufficiently long-an explicit expression for the respective critical shear rate is derived and compared to experimental data.

Breakup of bubbles and drops in steadily sheared foams and concentrated emulsions.

This experimental study is focused on the process of bubble breakup in steadily sheared foams, at constant shear rate or constant shear stress. Two different types of surfactants were used and glycerol was added to the aqueous phase, to check how the bubble breakup depends on the surface modulus and on bulk viscosity of the foaming solutions. The experiments show that bubble breakup in foams occurs above a well defined critical dimensionless stress, tau[over]CR identical with(tauCRR/sigma) approximately 0.40, which is independent of surfactant used, solution viscosity, and bubble volume fraction (varied between 92 and 98%). Here tauCR is the dimensional shear stress, above which a bubble with radius R and surface tension sigma would break in sheared foam. The value of the critical stress experimentally found by us tau[over]CR approximately 0.40, is about two orders of magnitude lower than the critical stress for breakup of single bubbles in sheared Newtonian liquids, tau[over]CR approximately 25. This large difference in the critical stress is explained by the strong interaction between neighboring bubbles in densely populated foams, which facilitates bubble subdivision into smaller bubbles. A strong effect of bubble polydispersity on the kinetics of bubble breakup (at similar mean bubble size) was observed and explained. Experiments were also performed with hexadecane-in-water emulsions of drop volume fraction 83%

Theoretical model of viscous friction inside steadily sheared foams and concentrated emulsions.

In a recent Letter [N. D. Denkov, Phys. Rev. Lett. 100, 138301 (2008)] we calculated theoretically the macroscopic viscous stress of steadily sheared foam or emulsion from the energy dissipated inside the transient planar films, formed between neighboring bubbles or drops in the shear flow. The model predicts that the viscous stress in these systems should be proportional to Ca 1/2, where Ca is a capillary number and n=1/2 is the power-law index. In the current paper we explain our model in detail and develop it further in several aspects: First, we extend the model to account for the effects of viscous friction in the curved meniscus regions, surrounding the planar films, on the dynamics of film formation and on the total viscous stress. Second, we consider the effects of surface forces (electrostatic, van der Waals, etc.) acting between the surfaces of the neighboring bubbles or drops and show that these forces could be important in emulsions, due to the relatively small thickness of emulsion films (often comparable to the range of action of surface forces). In contrast, the surface forces are usually negligible in steadily sheared foams, because the dynamic foam films are thicker than the extent of surface forces, except for foams containing micrometer-sized bubbles and/or at very low shear rates. Third, additional consideration is made for bubbles or drops exhibiting high surface viscosity, for which we demonstrate an additional contribution to the macroscopic viscous stress, created by the surface dissipation of energy. The new upgraded model predicts that the energy dissipation at the bubble or drop surface leads to power-law index n<1/2 , whereas the contribution of the surface forces leads to n>1/2 , which explains the rich variety of foam or emulsion behaviors observed upon steady shear. Various comparisons are made between model predictions and experimental results for both foams and emulsions, and very good agreement is found.

Surfactant mixtures for control of bubble surface mobility in foam studies.

A new class of surfactant mixtures is described, which is particularly suitable for studies related to foam dynamics, such as studies of foam rheology, liquid drainage from foams and foam films, and bubble coarsening and rearrangement. These mixtures contain an anionic surfactant, a zwitterionic surfactant, and fatty acids (e.g., myristic or lauric) of low concentration. Solutions of these surfactant mixtures exhibit Newtonian behavior, and their viscosity could be varied by using glycerol. Most importantly, the dynamic surface properties of these solutions, such as their surface dilatational modulus, strongly depend on the presence and on the chain-length of fatty acid(s). Illustrative results are shown to demonstrate the dependence of solution properties on the composition of the surfactant mixture, and the resulting effects on foam rheological properties, foam film drainage, and bubble Ostwald ripening. The observed high surface modulus in the presence of fatty acids is explained with the formation of a surface condensed phase of fatty acid molecules in the surfactant adsorption layer.

Viscous friction in foams and concentrated emulsions under steady shear.

We present a model for the viscous friction in foams and concentrated emulsions, subject to steady shear flow. First, we calculate the energy dissipated due to viscous friction inside the films between two neighboring bubbles or drops, which slide along each other in the flow. Next, from this energy we calculate the macroscopic viscous stress of the sheared foam or emulsion. The model predictions agree well with experimental results obtained with foams and emulsions.

Comparison of solid particles, globular proteins and surfactants as emulsifiers.

The aim of this paper is to present a short overview of the main mechanisms operative in the formation and stabilization of emulsions by solid particles and, on this basis, to make comparisons between solid particles, surfactants and globular proteins as emulsifiers. When available, simple quantitative relations are presented, with the respective numerical estimates and discussion of the applicability of these relations to particle-stabilized systems. Non-obvious similarities between the different types of emulsifiers are outlined in several cases in which the description of the system can be performed at a phenomenological level. Examples are presented for the process of emulsification, where we show that several simple theoretical expressions, derived originally in the studies of surfactants and protein emulsifiers, can be successfully applied to particle-stabilized emulsions. In contrast, for the phenomena in which the detailed mechanisms of particle adsorption and film stabilization are important, the differences between the various emulsifiers prevail, thus making it impossible to use the same theoretical description. The most important specific characteristics of the solid particles which strongly affect their behavior are the high barrier to particle adsorption, high desorption energy and strong capillary forces between particles trapped in liquid films, which all originate in the relatively large particle size (as compared to the size of surfactant and protein molecules). The capillary mechanism of stabilization of liquid films by solid particles is reviewed in some detail, to emphasize its specific features and to demonstrate the applicability of several simple expressions for approximate estimates. Interestingly, we found that the hypothesis for some exceptionally high coalescence stability of the particle-stabilized emulsions is not supported by the experimental data available in literature. On the other hand, the particles are able to completely arrest the process of Ostwald ripening in foams and emulsions, and this effect can be easily explained with the high desorption energy of the particles and the resulting capillary effects.

Interpretation of surface-tension isotherms of n-alkanoic (fatty) acids by means of the van der Waals model.

Here we apply the two-dimensional van der Waals model to interpret surface-tension isotherms of aqueous solutions of n-alkanoic (fatty) acids. We processed available experimental data for a homologous series of eight acids, from pentanoic to dodecanoic (lauric). Only three adjustable parameters have been varied to fit simultaneously all experimental curves. Excellent agreement between the theoretical model and the experiment has been obtained. The determined parameter values comply well with the molecular properties and allow one to calculate the surfactant adsorption, surface elasticity, and the surface pressure vs area isotherms. For the dodecanoic acid, the van der Waals model indicates the existence of a surface phase transition.

Latex-particle-stabilized emulsions of anti-Bancroft type.

Here, we investigate water-in-oil (W/O) emulsions that are stabilized by polystyrene latex particles with sulfate surface groups. The particles, which play the role of emulsifier, are initially contained in the disperse (water) phase. The existence of such emulsions formally contradicts the empirical Bancroft rule. Theoretical considerations predict that the drop diameter has to be inversely proportional to the particle concentration, but should be independent of the volume fraction of water. In addition, there should be a second emulsification regime, in which the drop diameter is determined by the input mechanical energy during the homogenization. The existence of these two regimes has been experimentally confirmed, and the obtained data agree well with the theoretical model. Stable W/O emulsions have been produced with hexadecane and tetradecane, while, in the case of more viscous and polar oils (soybean and silicone oil), the particles enter into the oily phase, and Pickering emulsions cannot be obtained. The formation of stable emulsions demands the presence of a relatively high concentration of electrolyte that lowers the electrostatic barrier to particle adsorption at the oil-water interface. Because the attachment of particles at the drop surfaces represents a kind of coagulation, it turns out that the Schulze-Hardy rule for the critical concentration of coagulation is applicable also to emulsification, which has been confirmed with suspensions containing Na(+), Mg(2+), and Al(3+) counterions. The increase of the particle and electrolyte concentrations and the decrease of the volume fraction of water are other factors that facilitate emulsification in the investigated system. To quantify the combined action of these factors, an experimental stability-instability diagram has been obtained.

Particle-interface interaction across a nonpolar medium in relation to the production of particle-stabilized emulsions.

Quantitative theory of the particle-interface interaction across a nonpolar medium is developed. We consider a spherical dielectric particle (phase 1), which is immersed in a nonpolar medium (phase 2), near its boundary with a third dielectric medium (phase 3). The interaction originates from electric charges at the particle surface (e.g., the surface of a silica particle immersed in oil). The theoretical problem is solved exactly, in terms of Legendre polynomials, for arbitrary values of the dielectric constants of the three phases. As a result, expressions for calculating the interaction force and energy are derived. These expressions generalize the known theory of the electrostatic image force (acing on point charges) to the case of particles that have finite size and uniform surface charge density. For typical parameter values (silica or glass particles immersed in tetradecane), the image-force interaction becomes significant for particles of radius R > 30 nm. At fixed relative particle-to-interface distance, the force increases with the cube of the particle radius. In general, this is a strong and long-range interaction. For micrometer-sized particles, the interaction energy could be on the order of 10(5) k(B)T at close contact, and, in addition, the interaction range could be about 10(5) particle radii. The sign of the interaction depends on the difference between the dielectric constants of phases 2 and 3. When phase 3 has a smaller dielectric constant (e.g., air), the interface repels the particle. In contrast, when phase 3 has a greater dielectric constant (e.g., water), the interaction is attractive. Especially, water drops attract charged hydrophobic particles dispersed in the oily phase, and thus favor the formation of reverse particle-stabilized (Pickering) emulsions. The particle-interface interaction across the oily phase is insensitive to the concentration of electrolyte in the third, aqueous phase.

Mass transport in micellar surfactant solutions: 2. Theoretical modeling of adsorption at a quiescent interface.

Here, we apply the detailed theoretical model of micellar kinetics from part 1 of this study to the case of surfactant adsorption at a quiescent interface, i.e., to the relaxation of surface tension and adsorption after a small initial perturbation. Our goal is to understand why for some surfactant solutions the surface tension relaxes as inverse-square-root of time, 1/t(1/2), but two different expressions for the characteristic relaxation time are applicable to different cases. In addition, our aim is to clarify why for other surfactant solutions the surface tension relaxes exponentially. For this goal, we carried out a computer modeling of the adsorption process, based on the general system of equations derived in part 1. This analysis reveals the existence of four different consecutive relaxation regimes (stages) for a given micellar solution: two exponential regimes and two inverse-square-root regimes, following one after another in alternating order. Experimentally, depending on the specific surfactant and method, one usually registers only one of these regimes. Therefore, to interpret properly the data, one has to identify which of these four kinetic regimes is observed in the given experiment. Our numerical results for the relaxation of the surface tension, micelle concentration and aggregation number are presented in the form of kinetic diagrams, which reveal the stages of the relaxation process. At low micelle concentrations, "rudimentary" kinetic diagrams could be observed, which are characterized by merging of some stages. Thus, the theoretical modeling reveals a general and physically rich picture of the adsorption process. To facilitate the interpretation of experimental data, we have derived convenient theoretical expressions for the time dependence of surface tension and adsorption in each of the four regimes.

Mass transport in micellar surfactant solutions: 1. Relaxation of micelle concentration, aggregation number and polydispersity.

The surfactant transfer in micellar solutions includes transport of all types of aggregates and the exchange of monomers between them. Such processes are theoretically described by a system containing tens of kinetic equations, which is practically inapplicable. For this reason, one of the basic problems of micellar kinetics is to simplify the general set of equations without loosing the adequacy and correctness of the theoretical description. Here, we propose a model, which generalizes previous models in the following aspects. First, we do not use the simplifying assumption that the width of the micellar peak is constant under dynamic conditions. Second, we avoid the use of the quasi-equilibrium approximation (local chemical equilibrium between micelles and monomers). Third, we reduce the problem to a self-consistent system of four nonlinear differential equations. Its solution gives the concentration of surfactant monomers, total micelle concentration, mean aggregation number, and halfwidth of the micellar peak as functions of the spatial coordinates and time. Further, we check the predictions of the model for the case of spatially uniform bulk perturbations (such as jumps in temperature, pressure or concentration). The theoretical analysis implies that the relaxations of the three basic parameters (micelle concentration, mean aggregation number, and polydispersity) are characterized by three different characteristic relaxation times. Two of them coincide with the slow and fast micellar relaxation times, which are known in the literature. The third time characterizes the relaxation of the width of the micellar peak (i.e. of the micelle polydispersity). It is intermediate between the slow and fast relaxation times, in the case of not-too-low micellar concentrations. For low micelle concentrations, the third characteristic time is close to the fast relaxation time. Procedure for obtaining the exact numerical solution of the problem is formulated. In addition, asymptotic analytical expressions are derived, which compare very well with the exact numerical solution. In the second part of this study, the obtained set of equations is applied for theoretical modeling of surfactant adsorption from micellar solutions under various dynamic conditions, corresponding to specific experimental methods.

On the thermodynamics of particle-stabilized emulsions: curvature effects and catastrophic phase inversion.

The flexural properties of a particle adsorption monolayer are investigated theoretically. If the particles are not densely packed, the interfacial bending moment and the spontaneous curvature (due to the particles) are equal to zero. The situation changes if the particles are closely packed. Then the particle adsorption monolayer possesses a significant bending moment, and the interfacial energies of bending and dilatation become comparable. In this case, the bending energy can either stabilize or destabilize the Pickering emulsion, depending on whether the particle contact angle is smaller or greater than 90 degrees . Theoretical expressions are derived for the bending moment, for the curvature elastic modulus, and for the work of interfacial deformation and emulsification. The latter is dominated by the work for creation of a new oil-water interface and by the work for particle adsorption. The curvature effects give a contribution of second order, which is significant only for emulsification at 50:50 water/oil volume fractions. A thermodynamic criterion for the type of the formed emulsion is proposed. It predicts the existence of a catastrophic phase inversion in particle-stabilized emulsions, in agreement with the experimental observations. The derived theoretical expressions could find application for interpretation of experimental data on production and stability of Pickering emulsions.

Mixed solutions of anionic and zwitterionic surfactant (Betaine): surface-tension isotherms, adsorption, and relaxation kinetics.

Here, we present experimental surface-tension isotherms of mixed solutions of two surfactants, sodium dodecyl sulfate (SDS) and cocoamidopropyl betaine (Betaine), measured by means of the Wilhelmy plate method. The kinetics of surface-tension relaxation exhibits two characteristic time scales, which have been distinguished to determine correctly the equilibrium surface tension. The transition from the zwitterionic to the cationic form of Betaine is detected by surface-tension measurements. Synergistic dependence of the critical micellization concentration on the composition of the surfactant blend is established. The experimental surface-tension isotherms are fitted by means of the two-component van der Waals model, and an excellent agreement between theory and experiment was achieved. Having determined the parameters of the model, we calculated different properties of the mixed surfactant adsorption layer at various concentrations ofSDS, Betaine, and salt. Such properties are the adsorptions ofthe two surfactants, the surface dilatational elasticity, the occupancy of the Stern layer by bound counterions, the surface electric potential, and so forth. In particular, the addition of a small amount of Betaine to SDS significantly increases the surface elasticity. The results could be further applied to predict the thickness and stability of foam films or the size of the rodlike micelles in the mixed solutions of SDS and Betaine.

Synergistic sphere-to-rod micelle transition in mixed solutions of sodium dodecyl sulfate and cocoamidopropyl betaine.

Static and dynamic light scattering experiments show that the mixed micelles of sodium dodecyl sulfate (SDS) and cocoamidopropyl betaine (CAPB) undergo a sphere-to-rod transition at unexpectedly low total surfactant concentrations, about 10 mM. The lowest transition concentration is observed at molar fraction 0.8 of CAPB in the surfactant mixture. The transition brings about a sharp increase in the viscosity of the respective surfactant solutions due to the growth of rodlike micelles. Parallel experiments with mixed solutions of CAPB and sodium laureth sulfate (sodium dodecyl-trioxyethylene sulfate, SDP3S) showed that the sphere-to-rod transition in SDP3S/CAPB mixtures occurs at higher surfactant concentrations, above 40 mM. The observed difference in the transition concentrations for SDS and SDP3S can be explained by the bulkier SDP3S headgroup. The latter should lead to larger mean area per molecule in the micelles containing SDP3S and, hence, to smaller spontaneous radius of curvature of the micelles (i.e., less favored transition from spherical to rodlike micelles). The static light scattering data are used to determine the mean aggregation number and the effective size of the spherical mixed SDS/CAPB micelles. From the dependence of the aggregation number on the surfactant concentration, the mean energy for transfer of a surfactant molecule from a spherical into a rodlike micelle is estimated.

Microemulsification of triglyceride sebum and the role of interfacial structure on bicontinuous phase behavior.

A unique triblock surfactant is reported that allows for the efficient microemulsification of triglycerides. Unlike the results of all previous efforts, these triglyceride microemulsions can be formed without the use of cosurfactants or dilution with co-oils and follow the classical patterns of surfactant phase behavior exhibited by mixtures of water, alkane oils, and nonionic oligoethylene glycol surfactants, i.e., progression from oil/water emulsions to one-phase microemulsions to water/oil emulsions with increasing temperature. Lamellar phases that usually dominate the aqueous phase behavior of surfactant/triglyceride mixtures are suppressed, allowing for the formation of single-phase microemulsions containing equal amounts of triglyceride and water. These isotropic and low-viscous fluids are particularly useful for cleansing and delivery of functional ingredients in skin care products. The effects of mixing a variety of typical skin care ingredients and components of sebum (skin oil) were also explored. Fatty acids significantly reduce the average microemulsion temperature, while other ingredients and oils, which do not partition at the oil/water interface, have less impact on the phase behavior. In all cases, one-phase microemulsions containing equal amounts of oil and water can be formed even at high additive concentrations. Indeed, partial replacement oftriglyceride with any of the additives examined consistently reduced the amount of surfactant necessary to form single-phase microemulsions. However, the greatest boost in surfactant efficiency was found with the addition of medium molecular weight amphiphilic block copolymers.