Interfacial thermodynamics and electrochemistry of protein partitioning in two-phase systems

The subject of this thesis is protein partition between an aqueous salt solution and a surface or an apolair liquid and the concomitant co-partition of small ions. The extent of co-partitioning determines the charge regulation in the protein partitioning process.Chapters 2 and 3 deal with phenomenological relations between the partition coefficient of the protein and the extent of the co- partition. The method of analysis is illustrated by some worked-out examples, using data taken either from literature or from chapter 5. The examples include proton titration curves, ion exchange chromatography, adsorption on colloidal particles and solubilization in reverse micelles. An important conclusion is that the partition process is subject to a rule, similar to the principle of Le Chatelier for chemical equilibria: if upon protein partitioning ions are expelled into the water phase, an increase of the ionic concentrations results in a decrease of the protein partition coefficient and conversely.A theory which allows for the prediction and molecular interpretation of the charge regulations is presented in chapter 4. The model describes the electrochemistry of a protein molecule through site binding of ions on a rigid surface. Although this is a considerably simplified picture of a real protein molecule, some aspects of the theory may be of general validity. One of them is the notion of the electrochemical adaptability of a charged colloidal particle, as measured by its intrinsic capacitance. In the case of a high intrinsic capacitance, a change in electrostatic interactions results in a large charge regulation whilst the surface potential remains almost constant. On the other hand, if the intrinsic capacitance is low, the particle resists externally imposed shifts in charge but does adapt its surface potential.Chapter 5 contains an experimental study towards understanding the mechanism of charge-regulation in protein adsorption. The system consists of crystals of the insoluble salt silver iodide as the adsorbent and the protein Bovine Serum Albumin as the adsorbate. By using a combined iodide and proton titration technique, the charges of the surface and the protein can be measured independently. We find that a negative surface induces a positive shift in the charge of the adsorbed protein. Opposed to intuitive expectation, the reverse is not always true: when the charge of the protein charge is maximallypositive, adsorption renders the silver iodide surface less negative.The anomalous charge regulation is explained in terms of the intrinsic capacitance of the adsorbed protein. The maximally positive protein cannot adapt its charge, and so the silver iodide surface is forced to adjust its charge completely to that of the protein. As the contact layer between adsorbed protein and the silver iodide crystal is electroneutral under almost all circumstances, the silver iodide surface must be as negative as the protein is positive. Hence, if the charge of the surface before adsorption is more negative than this value, adsorption of the protein is accompanied by a desorption of negative charge.The experimental results are well understood in view of the developed phenomenological theory and model analysis. Two thermodynamic relations are succesfully verified, indicating the internal consistency of the various experiments. Application of the model gives two independent estimates of the size of the adsorbed protein. It is concluded that the protein does not substantially modify its native structure upon adsorption

Stochastic quasi-Newton molecular simulations

Article / Letter to editorLeiden Institute of Chemistr

Morphology of symmetric block copolymer in a cylindrical pore

The influence of confinement on morphology formation in copolymer systems is an important area of interest in theoretical research. We apply dynamic density functional theory to investigate the effect of pores on the morphology formation in a symmetric diblock copolymer system. The pore is represented by a perfect cylindrical tube. Porous systems are important in biology and are gaining interest for applications in nanotechnology. We show that for the pore sizes under investigation two equilibrium morphologies are possible depending on the surface interaction: a perpendicular or slab morphology and a parallel or multiwall tube morphology. The latter is referred to in the article as dartboard morphology. In the dynamic pathway towards this morphology an intermediate metastable helical phase is found. An important observation is that, for a wide range of pore radii and variations of polymer chain length, no mixed parallel/perpendicular morphologies were found: All observed morphologies are insensitive to the pore diameter

Morphology of symmetric block copolymer in a cylindrical pore

The influence of confinement on morphology formation in copolymer systems is an important area of interest in theoretical research. We apply dynamic density functional theory to investigate the effect of pores on the morphology formation in a symmetric diblock copolymer system. The pore is represented by a perfect cylindrical tube. Porous systems are important in biology and are gaining interest for applications in nanotechnology. We show that for the pore sizes under investigation two equilibrium morphologies are possible depending on the surface interaction: a perpendicular or slab morphology and a parallel or multiwall tube morphology. The latter is referred to in the article as dartboard morphology. In the dynamic pathway towards this morphology an intermediate metastable helical phase is found. An important observation is that, for a wide range of pore radii and variations of polymer chain length, no mixed parallel/perpendicular morphologies were found: All observed morphologies are insensitive to the pore diameter

Stochastic quasi-Newton molecular simulations

Soft Matter Chemistr

Stochastic quasi-Newton method: Application to minimal model for proteins

Soft Matter Chemistr

Coarse-grained hybrid simulation of liposomes

Soft Matter Chemistr

Inverse mapping of block copolymer morphologies

Supramolecular & Biomaterials Chemistr

Spinodal Decomposition in a Binary Polymer Mixture: Dynamic Self Consistent Field Theory and Monte Carlo Simulations

We investigate how the dynamics of a single chain influences the kinetics of early stage phase separation in a symmetric binary polymer mixture. We consider quenches from the disordered phase into the region of spinodal instability. On a mean field level we approach this problem with two methods: a dynamical extension of the self consistent field theory for Gaussian chains, with the density variables evolving in time, and the method of the external potential dynamics where the effective external fields are propagated in time. Different wave vector dependencies of the kinetic coefficient are taken into account. These early stages of spinodal decomposition are also studied through Monte Carlo simulations employing the bond fluctuation model that maps the chains -- in our case with 64 effective segments -- on a coarse grained lattice. The results obtained through self consistent field calculations and Monte Carlo simulations can be compared because the time, length, and temperature scales are mapped onto each other through the diffusion constant, the chain extension, and the energy of mixing. The quantitative comparison of the relaxation rate of the global structure factor shows that a kinetic coefficient according to the Rouse model gives a much better agreement than a local, i.e. wave vector independent, kinetic factor. Including fluctuations in the self consistent field calculations leads to a shorter time span of spinodal behaviour and a reduction of the relaxation rate for smaller wave vectors and prevents the relaxation rate from becoming negative for larger values of the wave vector. This is also in agreement with the simulation results.Comment: Phys.Rev.E in prin