Superfluid Behavior of Active Suspensions from Diffusive Stretching.

The current understanding is that the non-Newtonian rheology of active matter suspensions is governed by fluid-mediated hydrodynamic interactions associated with active self-propulsion. Here we discover an additional contribution to the suspension shear stress that predicts both thickening and thinning behavior, even when there is no nematic ordering of the microswimmers with the imposed flow. A simple micromechanical model of active Brownian particles in homogeneous shear flow reveals the existence of off-diagonal shear components in the swim stress tensor, which are independent of hydrodynamic interactions and fluid disturbances. Theoretical predictions from our model are consistent with existing experimental measurements of the shear viscosity of active suspensions, but also suggest new behavior not predicted by conventional models.

Swim pressure: stress generation in active matter.

We discover a new contribution to the pressure (or stress) exerted by a suspension of self-propelled bodies. Through their self-motion, all active matter systems generate a unique swim pressure that is entirely athermal in origin. The origin of the swim pressure is based upon the notion that an active body would swim away in space unless confined by boundaries-this confinement pressure is precisely the swim pressure. Here we give the micromechanical basis for the swim stress and use this new perspective to study self-assembly and phase separation in active soft matter. The swim pressure gives rise to a nonequilibrium equation of state for active matter with pressure-volume phase diagrams that resemble a van der Waals loop from equilibrium gas-liquid coexistence. Theoretical predictions are corroborated by Brownian dynamics simulations. Our new swim stress perspective can help analyze and exploit a wide class of active soft matter, from swimming bacteria to catalytic nanobots to molecular motors that activate the cellular cytoskeleton.

Complex oscillatory yielding of model hard-sphere glasses.

The yielding behavior of hard sphere glasses under large-amplitude oscillatory shear has been studied by probing the interplay of Brownian motion and shear-induced diffusion at varying oscillation frequencies. Stress, structure and dynamics are followed by experimental rheology and Browian dynamics simulations. Brownian-motion-assisted cage escape dominates at low frequencies while escape through shear-induced collisions at high ones, both related with a yielding peak in G''. At intermediate frequencies a novel, for hard sphere glasses, double peak in G'' is revealed reflecting both mechanisms. At high frequencies and strain amplitudes a persistent structural anisotropy causes a stress drop within the cycle after strain reversal, while higher stress harmonics are minimized at certain strain amplitudes indicating an apparent harmonic response.

Anisotropic diffusion of concentrated hard-sphere colloids near a hard wall studied by evanescent wave dynamic light scattering.

Evanescent wave dynamic light scattering and Stokesian dynamics simulations were employed to study the dynamics of hard-sphere colloidal particles near a hard wall in concentrated suspensions. The evanescent wave averaged short-time diffusion coefficients were determined from experimental correlation functions over a range of scattering wave vectors and penetration depths. Stokesian dynamics simulations performed for similar conditions allow a direct comparison of both the short-time self- and collective diffusivity. As seen earlier [V. N. Michailidou, G. Petekidis, J. W. Swan, and J. F. Brady, Phys. Rev. Lett. 102, 068302 (2009)] while the near wall dynamics in the dilute regime slow down compared to the free bulk diffusion, the reduction is negligible at higher volume fractions due to an interplay between the particle-wall and particle-particle hydrodynamic interactions. Here, we provide a comprehensive comparison between experiments and simulations and discuss the interplay of particle-wall and particle-particle hydrodynamics in the self- and cooperative dynamics determined at different scattering wave vectors and penetration depths.

Yielding of hard-sphere glasses during start-up shear.

Concentrated hard-sphere suspensions and glasses are investigated with rheometry, confocal microscopy, and Brownian dynamics simulations during start-up shear, providing a link between microstructure, dynamics, and rheology. The microstructural anisotropy is manifested in the extension axis where the maximum of the pair-distribution function exhibits a minimum at the stress overshoot. The interplay between Brownian relaxation and shear advection as well as the available free volume determine the structural anisotropy and the magnitude of the stress overshoot. Shear-induced cage deformation induces local constriction, reducing in-cage diffusion. Finally, a superdiffusive response at the steady state, with a minimum of the time-dependent effective diffusivity, reflects a continuous cage breakup and reformation.

Chaos and threshold for irreversibility in sheared suspensions.

Systems governed by time reversible equations of motion often give rise to irreversible behaviour. The transition from reversible to irreversible behaviour is fundamental to statistical physics, but has not been observed experimentally in many-body systems. The flow of a newtonian fluid at low Reynolds number can be reversible: for example, if the fluid between concentric cylinders is sheared by boundary motion that is subsequently reversed, then all fluid elements return to their starting positions. Similarly, slowly sheared suspensions of solid particles, which occur widely in nature and science, are governed by time reversible equations of motion. Here we report an experiment showing precisely how time reversibility fails for slowly sheared suspensions. We find that there is a concentration dependent threshold for the deformation or strain beyond which particles do not return to their starting configurations after one or more cycles. Instead, their displacements follow the statistics of an anisotropic random walk. By comparing the experimental results with numerical simulations, we demonstrate that the threshold strain is associated with a pronounced growth in the Lyapunov exponent (a measure of the strength of chaotic particle interactions). The comparison illuminates the connections between chaos, reversibility and predictability.

Waves in active matter: The transition from ballistic to diffusive behavior.

We highlight the unique wavelike character observed in the relaxation dynamics of active systems via a Smoluchowski based theoretical framework and Brownian dynamic simulations. Persistent swimming motion results in wavelike dynamics until the advective swim displacements become sufficiently uncorrelated, at which point the motion becomes a random walk process characterized by a swim diffusivity, D^{swim}=U_{0}^{2}τ_{R}/[d(d-1)], dependent on the speed of swimming U_{0}, reorientation time τ_{R}, and reorientation dimension d. This change in behavior is described by a telegraph equation, which governs the transition from ballistic wavelike motion to long-time diffusive motion. We study the relaxation of active Brownian particles from an instantaneous source, and provide an explanation for the nonmonotonicity observed in the intermediate scattering function. Using our simple kinetic model we provide the density distribution for the diffusion of active particles released from a line source as a function of time, position, and the ratio of the activity to thermal energy. We extend our analysis to include the effects of an external field on particle spreading to further understand how reorientation events in the active force vector affect relaxation. The strength of the applied external field is shown to be inversely proportional to the decay of the wavelike structure. Our theoretical description for the evolution of the number density agrees with Brownian dynamic simulation data.

Effect of diallyl sulfide on rat liver microsomal nitrosamine metabolism and other monooxygenase activities.

It has been reported that p.o. administration of diallyl sulfide (DAS), a naturally occurring component of garlic (Allium sativum), inhibits 1,2-dimethylhydrazine-induced colon and liver cancer in rodents. A possible mechanism for this protective effect is inhibition of hepatic activation of the procarcinogen. The effect of DAS on P450IIE1, an isozyme of cytochrome P-450 which is active in the oxidative metabolism of dimethylhydrazine, was conveniently assayed in the present study by determination of N-dimethylnitrosamine demethylase (NDMAd) activity at 1 mM N-dimethylnitrosamine in Sprague-Dawley rat liver microsomal incubations. DAS was found to be a competitive inhibitor of NDMAd, in contrast to the irreversible inactivation of NDMAd produced by carbon tetrachloride incubated under similar conditions. The inhibition by DAS of the demethylation of several substrates was selective. The thioether was most potent against N-dimethylnitrosamine, less effective against N-nitrosomethylbenzylamine, and essentially ineffective against benzphetamine and ethylmorphine. Microsomes prepared at 3 h after DAS administration (200 mg/kg in corn oil intragastrically) showed moderate inhibition (less than 30% inhibition compared to control microsomes) of several demethylase activities; however, microsomes prepared 18 h posttreatment showed a marked decrease (about 80% inhibition compared to controls) in NDMAd activity, minor effects on other demethylase activities, and a 6-fold increase in pentoxyresorufin dealkylation. These trends at 18 h agreed with immunoblot analyses which showed suppression in the level of P450IIE1 and an elevation in P450IIB1. The selective inhibition of P450IIE1 activity and suppression of its level in microsomes may contribute to the reported chemoprotective effects of DAS.

Substrate specificity and alkyl group selectivity in the metabolism of N-nitrosodialkylamines.

Metabolic activation may be a key step in determining the tissue specificity of carcinogenic nitrosamines. In previous work, we characterized P450IIE1 (an acetone/ethanol-inducible form of cytochrome P-450) as the major enzyme for the metabolic activation of N-nitrosodimethylamine. In this work, we investigated the metabolism of other N-nitrosodialkylamines in rat liver microsomes and in reconstituted monooxygenase systems containing purified cytochrome P-450 isozymes. The enzyme specificities in the metabolism of N-nitrosoethylmethylamine and N-nitrosodiethylamine were similar to those of N-nitrosodimethylamine; i.e., these substrates were more efficiently metabolized by acetone- or ethanol-induced microsomes than by other types of microsomes. However, substituting one methyl group with a benzyl or butyl group, as in N-nitrosobenzylmethylamine or N-nitrosobutylmethylamine (NBMA), substantially changed the enzyme specificity. P450IIE1 efficiently catalyzed the demethylation but not the debutylation of NBMA, whereas P450IIB1 (a phenobarbital-inducible form) efficiently catalyzed both the debutylation and demethylation reactions. In the demethylation of NBMA by P450IIE1, the addition of cytochrome b5 markedly increased the activity at low but not at high substrate concentrations, suggesting a decrease in Km value. This effect, however, was not observed in the debutylation of NBMA by P450IIE1 or P450IIB1, and in the demethylation of NBMA by P450IIB1. These studies demonstrate the substrate specificity and alkyl group selectivity in the metabolism of nitrosamines by cytochrome P-450 isozymes.

Metabolism of carcinogenic nitrosamines by rat nasal mucosa and the effect of diallyl sulfide.

Rat nasal cavity is one of the target organs for carcinogenesis induced by N-nitrosodimethylamine (NDMA), N-nitrosodiethylamine (NDEA), and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). The present work investigated the metabolism of these nitrosamines by rat nasal microsomes, as well as the possible modulating factors. Microsomes prepared from rat nasal mucosa were efficient in metabolizing these nitrosamines. In general, the metabolism of the nitrosamines was slightly higher in 9-week-old rats than in 4-week-old animals, and there was no sex-related difference. Fasting of rats for 48 h, which is known to induce hepatic cytochrome P450IIE1 and NDMA metabolism, did not increase the nasal metabolism of NDMA, NDEA, or NNK. Pretreatment of rats with acetone, another inducer of hepatic P450IIE1, did not increase the metabolism of NDMA. Furthermore, it decreased the nasal metabolism of NDEA and NNK. Immunoinhibition studies suggest that, in the nasal mucosa, P450IIE1 is only partially responsible for the oxidation of NDMA and other P450 isozymes are responsible for the metabolism of NDEA. A single p.o. pretreatment of male rats with diallyl sulfide (DAS), a component of garlic oil, caused a significant decrease in the oxidative metabolism of NDEA and NNK in rat nasal mucosa. Whereas the nasal metabolism of NDMA was reduced by DAS pretreatment, there was no change in the amount of the nasal microsomal proteins immunoreactive with the antibodies against P450IIE1. The inhibitory effect of DAS on the nasal oxidative metabolism of NDMA, NDEA, and NNK was also observed in experiments in vitro. The results demonstrate the ability of nasal mucosa to metabolically activate these nitrosamines and the inhibition of this process by DAS, suggesting that DAS may be effective in inhibiting the related nasal tumorigenesis.

Towards a thermodynamics of active matter.

Self-propulsion allows living systems to display self-organization and unusual phase behavior. Unlike passive systems in thermal equilibrium, active matter systems are not constrained by conventional thermodynamic laws. A question arises, however, as to what extent, if any, can concepts from classical thermodynamics be applied to nonequilibrium systems like active matter. Here we use the new swim pressure perspective to develop a simple theory for predicting phase separation in active matter. Using purely mechanical arguments we generate a phase diagram with a spinodal and critical point, and define a nonequilibrium chemical potential to interpret the "binodal." We provide a generalization of thermodynamic concepts like the free energy and temperature for nonequilibrium active systems. Our theory agrees with existing simulation data both qualitatively and quantitatively and may provide a framework for understanding and predicting the behavior of nonequilibrium active systems.

Spectral and inhibitory interactions of (+/-)-3,4-methylenedioxyamphetamine (MDA) and (+/-)-3,4-methylenedioxymethamphetamine (MDMA) with rat hepatic microsomes.

Incubation of racemic methylenedioxyamphetamine (MDA) or methylenedioxymethamphetamine (MDMA) with rat hepatic microsomes, in the presence of NADPH, generated a spectrally observed inhibitory complex with cytochrome P-450. The complex inhibited product formation from MDA and MDMA as well as other P-450 dependent reactions such as benzphetamine demethylation and CO binding. In the absence of NADPH, MDMA and MDA generated type I and type IIa difference spectra, respectively, suggesting differences in their binding to the enzyme active site. The N-demethylation of MDMA was partially inhibited by methimazole suggesting involvement of the hepatic flavin-containing monooxygenase.

Effect of 1,3-butanediol on rat liver microsomal NDMA demethylation and other monooxygenase activities.

The administration of 1,3-butanediol (BD) previously has been shown to elevate blood concentrations of ketone bodies, to potentiate carbon tetrachloride hepatotoxicity, and to increase the hepatic microsomal content of cytochrome P450 and the activity of aniline hydroxylase. In the present study, oral treatment (10 g/kg) with racemic BD and each of its enantiomers (R-BD and S-BD) induced NDMA demethylase activity by approx. 1.5-fold in rat hepatic microsomes obtained 12 h later, suggesting an induction of P450IIE1, the acetone/ethanol-inducible form of P450. The results agreed with an immunochemically determined increase in the levels of this isozyme. No change in P450 content, NADPH-cytochrome-c reductase, or in pentoxyresorufin dealkylase activity were detected. Blood levels of acetone were determined during a 10-h period after BD administration and showed a higher initial rate of increase by R-BD, possibly due to steroselective metabolic oxidative metabolism. However, no difference in the induction of NDMA demethylase activity by the enantiomers could be detected. Induction of P450IIE1 probably contributes to the previously described potentiation of haloalkane-induced hepatotoxicity by BD administration.

Short- and intermediate-time behavior of the linear stress relaxation in semiflexible polymers.

The linear viscoelasticity of semiflexible polymers is studied through Brownian Dynamics simulations covering a broad range of chain stiffness and time scales. Our results agree with existing theoretical predictions in the flexible and stiff limits; however, we find that over a wide intermediate-time window spanning several decades, the stress relaxation is described by a single power law t(-alpha), with the exponent alpha apparently varying continuously from 1/2 for flexible chains, to 5/4 for stiff ones. Our study identifies the limits of validity of the t(-3/4) power law at short times predicted by recent theories. An additional regime is identified, the "ultrastiff" chains, where this behavior disappears. In the absence of Brownian motion, the purely mechanical stress relaxation produces a t(-3/4) power law for both short and intermediate times.

A BASIC program for the estimation of Michaelis-Menten parameters by the direct linear plot.

The use of manual graphical methods for the estimation of Michaelis-Menten kinetic parameters as recommended by Eisenthal and Cornish-Bowden (Biochem. J. 139 (1974) 715-720) was found to be impractical for large (n greater than 5) sample numbers. A BASIC program providing the rank ordered coordinates of intersections, which correspond to estimates of Km and Vmax in the direct linear plot method, is described.

Transient dynamics in dense colloidal suspensions under shear: shear rate dependence.

A combination of confocal microscopy and rheology experiments, Brownian dynamics (BD) and molecular dynamics (MD) simulations and mode coupling theory (MCT) have been applied in order to investigate the effect of shear rate on the transient dynamics and stress-strain relations in supercooled and glassy systems under shear. Immediately after shear is switched on, the microscopic dynamics display super-diffusion and the macroscopic rheology a stress overshoot, which become more pronounced with increasing shear rate. MCT relates both to negative sections of the generalized shear modulus, which grow with increasing shear rate. When the inverse shear rate becomes much smaller than the structural relaxation time of the quiescent system, relaxation through Brownian motion becomes less important. In this regime, larger stresses are accumulated before the system yields and the transition from localization to flow occurs earlier and more abruptly.

Dynamics of concentrated hard-sphere colloids near a wall.

We investigate the Brownian motion of hard-sphere colloids near a solid wall by Evanescent Wave Dynamic Light Scattering (EWDLS). We carried out measurements for various volume fractions of sterically stabilized poly(methyl methacrylate) (PMMA) particles over a range of scattering wave vectors, q. While in the dilute regime, the near wall short-time diffusion is significantly slowed down due to particle-wall hydrodynamic interactions (HI); as volume fraction increases, the wall effect is progressively diminished at all q's. We present a new analysis for the EWDLS short-time self- and collective diffusivities applicable to all volume fractions and a simple model for the self-diffusion describing the interplay between particle-wall and particle-particle HI. Moreover, a weaker decay of the near-wall self-diffusion coefficient with volume fraction is predicted by Stokesian dynamics simulations.

Effect of level of dietary protein on arginine-stimulated citrulline synthesis. Correlation with mitochondrial N-acetylglutamate concentrations.

Increases in dietary protein have been reported to increase the rate of citrulline synthesis and the level of N-acetylglutamate in liver. We have confirmed this effect of diet on citrulline synthesis in rat liver mitochondria and show parallel increases in N-acetylglutamate concentration. The magnitude of the effect of arginine in the suspending medium on citrulline synthesis was also dependent on dietary protein content. Mitochondria from rats fed on a protein-free diet initially contained low levels of N-acetylglutamate, and addition of arginine increased the rate of its synthesis. Citrulline synthesis and acetylglutamate content in these mitochondria increased more than 5-fold when 1 mM-arginine was added. A diet high in protein results in mitochondria with increased N-acetylglutamate and a high rate of citrulline synthesis; 1 mM-arginine increased citrulline synthesis in such mitochondria by only 36%. The concentration of arginine in portal blood was 47 microM in rats fed on a diet lacking protein, and 182 microM in rats fed on a diet containing 60% protein, suggesting that arginine may be a regulatory signal to the liver concerning the dietary protein intake. The rates of citrulline synthesis were proportional to the mitochondrial content of acetylglutamate in mitochondria obtained from rats fed on diets containing 0, 24, or 60% protein, whether incubated in the absence or presence of arginine. Although the effector concentrations are higher than the Ka for the enzymes, these results support the view that concentrations of both arginine and acetylglutamate are important in the regulation of synthesis of citrulline and urea. Additionally, the effects of dietary protein level (and of arginine) are exerted in large part by way of modulation of the concentration of acetylglutamate.