Tuning cell adhesion on gradient poly(2-hydroxyethyl methacrylate)-grafted surfaces

A simple yet versatile method was developed to prepare a low-density polymerization initiator gradient, which was combined with surface-initiated atom transfer radical polymerization (ATRP) to produce a well-defined poly(2-hydroxyethyl methacrylate) (HEMA) gradient substrate. A smooth variation in film thickness was measured across the gradient, ranging from 20 A to over 80 A, but we observed a nonmonotonic variation in water contact angle. Fits of X-ray reflectivity profiles suggested that at the low graft density end, the polymer chain structure was in a "mushroom" regime, while the polymer chains at high graft density were in a "brush" regime. It was found that the "mushroom" region of the gradient could be made adhesive to cells by adsorbing adhesion proteins, and cell adhesion could be tuned by controlling the density of the polymer grafts. Fibroblasts were seeded on gradients precoated with fibronectin to test cellular responses to this novel substrate, but it was found that cell adhesion did not follow the expected trend; instead, saturated cell adhesion and spreading was found at the low grafting density region.     

The minicellirradiator: A new system for a new market

Since the commissioning of the first industrial Gamma Irradiator design, designers and operators of irradiation systems have been attempting to meet the specific production requirements and challenges presented to them. This objective has resulted in many different versions of irradiators currently in service today, all of which had original charters and many of which still perform very well within even the new requirements of this industry.

Continuing changes in the marketplace have, however, placed pressures on existing designs due to a combination of changing dose requirements for sterlization, increased economic pressures from the specific industry served for both time and location and the increasing variety of product types requiring processing. Additionally, certain market areas which could never economically support a typical gamma processing facility have either not been serviced, or have forced potential gamma users to transport product long distances to one of these existing facilities.

The MiniCell^TM removes many of the traditional barriers previously accepted in the radiation processing industry for building a processing facility in a location. Its reduced size and cost have allowed many potential users to consider in-house processing and its ability to be quickly assembled allow it to meet market needs in a much more timely fashion than the previous designs.

The MiniCell system can cost effectively meet many of the current market needs of reducing total cost of processing and also be flexible enough to process product in a wide range of industries effectively.     

Polymer contribution to the thermal conductivity and viscosity in a dilute solution (Fraenkel Dumbbell model)

The phase-space kinetic theory for polymeric liquid mixtures is used to obtain an expression for the polymer contribution to the thermal conductivity of a nonflowing, dilute solution of polymers, where the polymer molecules are modeled as Fraenkel dumbbells. This theory takes into account three mechanisms for the energy transport: diffusion of kinetic energy (including the Öttinger-Petrillo term), diffusion of intramolecular energy, and the work done against the intramolecular forces. This paper is an extension of previous developments for the Hookean dumbbell model and the finitely-extensible dumbbell model. A comparison among the dumbbell results suggests that the thermal conductivity increases with chain stiffness. In addition, the zero-shear-rate viscosity and first normal-stress coefficient are also given for the Fraenkel dumbbell model.Dedicated to Prof. John D. Ferry on the occasion of his 85th birthday.     

Continuous flow enzyme-catalyzed polymerization in a microreactor

Enzymes immobilized on solid supports are increasingly used for greener, more sustainable chemical transformation processes. Here, we used microreactors to study enzyme-catalyzed ring-opening polymerization of ε-caprolactone to polycaprolactone. A novel microreactor design enabled us to perform these heterogeneous reactions in continuous mode, in organic media, and at elevated temperatures. Using microreactors, we achieved faster polymerization and higher molecular mass compared to using batch reactors. While this study focused on polymerization reactions, it is evident that similar microreactor based platforms can readily be extended to other enzyme-based systems, for example, high-throughput screening of new enzymes and to precision measurements of new processes where continuous flow mode is preferred. This is the first reported demonstration of a solid supported enzyme-catalyzed polymerization reaction in continuous mode.     

Kriging for interpolation in random simulation

Whenever simulation requires much computer time, interpolation is needed. Simulationists use different interpolation techniques (eg linear regression), but this paper focuses on Kriging. This technique was originally developed in geostatistics by DG Krige, and has recently been widely applied in deterministic simulation. This paper, however, focuses on random or stochastic simulation. Essentially, Kriging gives more weight to ‘neighbouring’ observations. There are several types of Kriging; this paper discusses—besides Ordinary Kriging—a novel type, which ‘detrends’ data through the use of linear regression. Results are presented for two examples of input/output behaviour of the underlying random simulation model: Ordinary and Detrended Kriging give quite acceptable predictions; traditional linear regression gives the worst results.     

Determination of the interfacial characteristics of a series of bolaamphiphilic poly(fluorooxetane) surfactants through molecular dynamics simulation

Constant surface tension (NgammaT) and constant volume (NVT) molecular dynamics simulations have been conducted on a series of bolaamphiphilic alpha,varpi-(diammonium disulfato)poly(fluorooxetane)s and on a typical "long-chain" anionic fluorosurfactant used to improve the flow-and-leveling characteristics of aqueous coatings, to compare their behavior at a water/air interface. Recent research has shown that the poly(fluorooxetane) surfactants considered in this paper could serve as an effective substitute for traditional fluorosurfactants used in flow-and-leveling applications.(1) From molecular dynamics simulation, we have determined the saturated interfacial area per surfactant, interfacial area per surfactant as a function of surface tension, density profiles, the degree of hydration for various atoms in each surfactant, the degree of counterion binding, and order parameters. Our results for saturated interfacial area per surfactant molecule are greater than what has been obtained by other researchers through parametric fitting of interfacial area from experimental surface tension data using the Davies isotherm. Possible explanations for this difference are discussed. The low interfacial areas occupied by each poly(fluorooxetane) at the water/air interface are the result of their ability to adopt a "looped" conformation, in which the carbon and oxygen backbone of each surfactant and the attached perfluoroalkyl chains are forced into the air phase. A geometrically defined penetration parameter was calculated from the density profiles, which reveals that each poly(fluorooxetane) surfactant is more effective at separating the air and water phases than the "long-chain" anionic fluorosurfactant. The degree of hydration measured for different atoms in poly(fluorooxetane) during simulation confirms that a "looped" conformation is adopted in which the surfactant backbone and the perfluoroalkyl chains are lifted away from the water surface. Calculation of order parameters revealed a much lower degree of ordering for the perfluoroalkyl side chains in each bolaamphiphile than in the "long chain" anionic fluorosurfactant. When viewed in the context of the penetration parameter analysis, the density profiles and hydration data suggest why each poly(fluorooxetane) is capable of significantly reducing surface tension when other fluorosurfactants with similarly short perfluoroalkyl moieties provide inadequate surface tension reduction for practical flow-and-leveling applications.     

Monotonicity-preserving bootstrapped Kriging metamodels for expensive simulations

Kriging metamodels (also called Gaussian process or spatial correlation models) approximate the Input/Output functions implied by the underlying simulation models. Such metamodels serve sensitivity analysis, especially for computationally expensive simulations. In practice, simulation analysts often know that this Input/Output function is monotonic. To obtain a Kriging metamodel that preserves this characteristic, this article uses distribution-free bootstrapping assuming each input combination is simulated several times to obtain more reliable averaged outputs. Nevertheless, these averages still show sampling variation, so the Kriging metamodel does not need to be an exact interpolator; bootstrapping gives a noninterpolating Kriging metamodel. Bootstrapping may use standard Kriging software. The method is illustrated through the popular M/M/1 model with either the mean or the 90% quantile as output; these outputs are monotonic functions of the traffic rate. The empirical results demonstrate that monotonicity-preserving bootstrapped Kriging gives higher probability of covering the true outputs, without lengthening the confidence interval.     

Application of computer simulation free-energy methods to compute the free energy of micellization as a function of micelle composition. 1. Theory

The widespread use of surfactant mixtures and surfactant/solubilizate mixtures in practical applications motivates the development of predictive theoretical approaches to improve fundamental understanding of the behavior of these complex self-assembling systems and to facilitate the design and optimization of new surfactant and surfactant/solubilizate mixtures. This paper is the first of two articles introducing a new computer simulation-free-energy/molecular thermodynamic (CS-FE/MT) model. The two articles explore the application of computer simulation free-energy methods to quantify the thermodynamics associated with mixed surfactant/cosurfactant and surfactant/solubilizate micelle formation in aqueous solution. In this paper (article 1 of the series), a theoretical approach is introduced to use computer simulation free-energy methods to compute the free-energy change associated with changing micelle composition (referred to as DeltaDeltaGi). In this approach, experimental critical micelle concentration (CMC) data, or a molecular thermodynamic model of micelle formation, is first used to evaluate the free energy associated with single (pure) surfactant micelle formation, g(form,single), in which the single surfactant micelle contains only surfactant A molecules. An iterative approach is proposed to combine the estimated value of gform,single with free-energy estimates of DeltaDeltaGi based on computer simulation to determine the optimal free energy of mixed micelle formation, the optimal micelle aggregation number and composition, and the optimal bulk solution composition. After introducing the CS-FE/MT modeling framework, a variety of free-energy methods are briefly reviewed, and the selection of the thermodynamic integration free-energy method is justified and selected to implement the CS-FE/MT model. An alchemical free-energy pathway is proposed to allow evaluation of the free-energy change associated with exchanging a surfactant A molecule with a surfactant/solubilizate B molecule through thermodynamic integration. In article 2 of this series, the implementation of the CS-FE/MT model to make DeltaDeltaGi free-energy predictions for several surfactant/solubilizate systems is discussed, and the predictions of the CS-FE/MT model are compared with the DeltaDeltaGi predictions of a molecular thermodynamic model fitted to relevant experimental data.     

Application of computer simulation free-energy methods to compute the free energy of micellization as a function of micelle composition. 2. Implementation

In this paper, the implementation of the CS-FE/MT model introduced in article 1 is discussed, and computer simulations are performed to evaluate the feasibility of the new theoretical approach. As discussed in article 1, making predictions of surfactant/solubilizate aqueous solution behavior using the CS-FE/MT model requires evaluation of DeltaDeltaG for multiple surfactant-to-solubilizate or surfactant-to-cosurfactant transformations. The central goal of this article is to evaluate the quantitative accuracy of the alchemical computer simulation method used in the CS-FE/MT modeling approach to predict DeltaDeltaG for a single surfactant-to-solubilizate or for a single surfactant-to-cosurfactant transformation. A hybrid single/dual topology approach was used to morph the ionic surfactant sodium dodecyl sulfate (SDS) into the ionic solubilizate ibuprofen (IBU), and a dual topology approach was used to morph the nonionic surfactant octyl glucoside (OG) into the nonionic solubilizate p-aminobenzoate (PAB). In addition, a single topology approach was used to morph the nonionic surfactant n-decyl dimethylphosphine oxide (C10PO) into the nonionic cosurfactant n-decyl methyl sulfoxide (C10SO), the nonionic surfactant octylsulfinyl ethanol (C8SE) into the nonionic cosurfactant decylsulfinyl ethanol (C10SE), and the nonionic surfactant n-decyl methyl sulfoxide (C10SO) into the nonionic cosurfactant n-octyl methyl sulfoxide (C8SO). Each DeltaDeltaG value was computed by using thermodynamic integration to determine the difference in free energy associated with (i) transforming a surfactant molecule of type A into a cosurfactant/solubilizate molecule of type B in a micellar environment (referred to as DeltaG2) and (ii) transforming a surfactant molecule of type A into a cosurfactant/solubilizate molecule of type B in aqueous solution (referred to as DeltaG1). CS-FE/MT model predictions of DeltaDeltaG for each alchemical transformation were made at a number of simulation conditions, including (i) different equilibration times at each value of the coupling parameter lambda, (ii) different data-gathering times at each lambda value, and (iii) simulation at a different number of lambda values. For the three surfactant-to-cosurfactant transformations considered here, the DeltaDeltaG values predicted by the CS-FE/MT model were compared with DeltaDeltaG values predicted by an accurate molecular thermodynamic (MT) model developed by fitting to experimental CMC data. Even after performing lengthy equilibration and data gathering at each lambda value, physically unrealistic values of DeltaDeltaG were predicted by the CS-FE/MT model for the transformations of SDS into IBU and of OG into PAB. However, more physically realistic DeltaDeltaG values were predicted for the transformation of C10PO into C10SO, and reasonable free-energy predictions were obtained for the transformations of C8SE into C10SE and C10SO into C8SO. Each of the surfactant-to-cosurfactant transformations considered here involved less extensive structural changes than the surfactant-to-solubilizate transformations. As computer power increases and as improvements are made to alchemical free-energy methods, it may become possible to apply the CS-FE/MT model to make accurate predictions of the free-energy changes associated with forming multicomponent surfactant and solubilizate micelles in aqueous solution where the chemical structures of the surfactants, cosurfactants, and solubilizates differ significantly.     

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. Although this hybrid method improves the accuracy of the MT approach for complex solutes with a minimum of computational expense, the limitation remains that individual atoms are modeled as being in only one of two states-head or tail-whereas in reality, there is a continuous spectrum of hydration states between these two limits. In the case of hydrophobic or amphiphilic solutes possessing more complex chemical structures, a new modeling approach is needed to (i) obtain quantitative information about changes in hydration that occur upon aggregate formation, (ii) quantify the hydrophobic driving force for self-assembly, and (iii) make predictions of micellization and micellar solubilization behavior. This article is the first in a series of articles introducing a new computer simulation-molecular thermodynamic (CS-MT) model that accomplishes objectives (i)-(iii) and enables prediction of micellization and micellar solubilization behaviors, which are infeasible to model directly using atomistic simulation. In this article (article 1 of the series), the CS-MT model is introduced and implemented to model simple oil aggregates of various shapes and sizes, and its predictions are compared to those of the traditional MT model. The CS-MT model is formulated to allow the prediction of the free-energy change associated with aggregate formation (gform) of solute aggregates of any shape and size by performing only two computer simulations-one of the solute in bulk water and the other of the solute in an aggregate of arbitrary shape and size. For the 15 oil systems modeled in this article, the average discrepancy between the predictions of the CS-MT model and those of the traditional MT model for gform is only 1.04%. In article 2, the CS-MT modeling approach is implemented to predict the micellization behavior of nonionic surfactants; in article 3, it is used to predict the micellization behavior of ionic and zwitterionic surfactants.