Elevated GM-CSF and IL-1beta levels compromise the ability of p38 MAPK inhibitors to modulate TNFalpha levels in the human monocytic/macrophage U937 cell line.

Rheumatoid arthritis (RA) is a complex, multicellular disease involving a delicate balance between both pro- and anti-inflammatory cytokines which ultimately determines the disease phenotype. The simultaneous presence of multiple signaling molecules, and more specifically their relative levels, potentially influences the efficacy of directed therapies. Using the human U937 monocytic cell line, we generated a self-consistent dataset measuring 50 cytokines and 23 phosphoproteins in the presence of 6 small molecule inhibitors under 15 stimulatory conditions throughout a 24 hour time course.

Association (micellization) and partitioning of aglycon triterpenoids.

Micellization and solution properties of the aglycon triterpenoids asiatic acid (AA) and madecassic acid (MA) were examined experimentally and in computational simulations. AA and MA belong to the large class of bioactive aglycon triterpenoids, for which limited physicochemical data are available. In this study, solubility, partition coefficient, critical micelle concentrations (CMC), and surface tensions of AA and MA were measured.

Molecular dynamics simulation and thermodynamic modeling of the self-assembly of the triterpenoids asiatic acid and madecassic acid in aqueous solution.

The self-assembly behavior of the triterpenoids asiatic acid (AA) and madecassic acid (MA), both widely studied bioactive phytochemicals that are similar in structure to bile salts, were investigated in aqueous solution through atomistic-level molecular dynamics (MD) simulation. AA and MA molecules initially distributed randomly in solution were observed to aggregate into micelles during 75 ns of MD simulation. A "hydrophobic contact criterion" was developed to identify micellar aggregates from the computer simulation results.

Flexible informatics for linking experimental data to mathematical models via DataRail.

Motivation: Linking experimental data to mathematical models in biology is impeded by the lack of suitable software to manage and transform data. Model calibration would be facilitated and models would increase in value were it possible to preserve links to training data along with a record of all normalization, scaling, and fusion routines used to assemble the training data from primary results.

Results: We describe the implementation of DataRail, an open source MATLAB-based toolbox that stores experimental data in flexible multi-dimensional arrays, transforms arrays so as to maximize information content, and then constructs models using internal or external tools.

Molecular-thermodynamic theory of micellization of multicomponent surfactant mixtures: 2. pH-sensitive surfactants.

In article 1 of this series, we developed a molecular-thermodynamic (MT) theory to model the micellization of mixtures containing an arbitrary number of conventional (pH-insensitive) surfactants. In this article, we extend the MT theory to model mixtures containing a pH-sensitive surfactant. The MT theory was validated by examining mixtures containing both a pH-sensitive surfactant and a conventional surfactant, which effectively behave like ternary surfactant mixtures.

Molecular-thermodynamic theory of micellization of multicomponent surfactant mixtures: 1. Conventional (pH-Insensitive) surfactants.

A molecular-thermodynamic (MT) theory was developed to model the micellization of mixtures containing an arbitrary number of conventional (pH-insensitive) surfactants. The theory was validated by comparing predicted and experimental cmc's of ternary surfactant mixtures, yielding results that were comparable to, and sometimes better than, the cmc's determined using regular solution theory. The theory was also used to model a commercial nonionic surfactant (Genapol UD-079), which was modeled as a mixture of 16 surfactant components.

Quantifying the hydrophobic effect. 2. A computer simulation-molecular-thermodynamic model for the micellization of nonionic surfactants in aqueous solution.

In this article, the validity and accuracy of the CS-MT model is evaluated by using it to model the micellization behavior of seven nonionic surfactants in aqueous solution. Detailed information about the changes in hydration that occur upon the self-assembly of the surfactants into micelles was obtained through molecular dynamics simulation and subsequently used to compute the hydrophobic driving force for micelle formation. This information has also been used to test, for the first time, approximations made in traditional molecular-thermodynamic modeling.

Quantifying the hydrophobic effect. 1. A computer simulation-molecular-thermodynamic model for the self-assembly of hydrophobic and amphiphilic solutes in aqueous solution.

Surfactant micellization and micellar solubilization in aqueous solution can be modeled using a molecular-thermodynamic (MT) theoretical approach; however, the implementation of MT theory requires an accurate identification of the portions of solutes (surfactants and solubilizates) that are hydrated and unhydrated in the micellar state. For simple solutes, such identification is comparatively straightforward using simple rules of thumb or group-contribution methods, but for more complex solutes, the hydration states in the micellar environment are unclear. Recently, a hybrid method was reported by these authors in which hydrated and unhydrated states are identified by atomistic simulation, with the resulting information being used to make MT predictions of micellization and micellar solubilization behavior.

Titration of mixed micelles containing a pH-sensitive surfactant and conventional (pH-Insensitive) surfactants: a regular solution theory modeling approach.

We present a thermodynamic theory to model the hydrogen-ion titration of mixed micelles containing a pH-sensitive surfactant and any number of conventional (pH-insensitive) surfactants. In particular, a simple expression is derived for the pKm, a parameter analogous to the pKa of simple acids, which describes the deprotonation equilibrium of the micellized pH-sensitive surfactant. The pseudophase approximation and regular solution theory (RST) are used to relate the pKm to (1) the pKa of the surfactant monomers, (2) the critical micelle concentrations (cmc's) of the protonated and deprotonated forms of the pH-sensitive surfactant, (3) the composition of the mixed micelle, and (4) parameters characterizing pairwise interactions between the surfactant molecules in the mixed micelle.

Molecular-thermodynamic theory of micellization of pH-sensitive surfactants.

A predictive, molecular-thermodynamic theory is developed to model the micellization of pH-sensitive surfactants. The theory combines a molecular-thermodynamic description of micellization in binary surfactant mixtures with the protonation equilibrium of the surfactant monomers. The thermodynamic component of the theory models the pH-mediated equilibrium between micelles, surfactant monomers, and counterions.

Modeling counterion binding in ionic-nonionic and ionic-zwitterionic binary surfactant mixtures.

A predictive molecular-thermodynamic theory is developed to model the effect of counterion binding on micellar solution properties of binary surfactant mixtures of ionic and nonionic (or zwitterionic) surfactants. The theory combines a molecular-thermodynamic description of micellization in binary surfactant mixtures with a recently developed model of counterion binding to single-component ionic surfactant micelles. The thermodynamic component of the theory models the equilibrium between the surfactant monomers, the counterions, and the mixed micelles.