Mathias Boström

Specific Ion Effects: Why the Properties of Lysozyme in Salt Solutions Follow a Hofmeister Series

Protein solubility in aqueous solutions depends in a complicated and not well understood way on pH, salt type, and salt concentration. Why for instance does the use of two different monovalent salts, potassium thiocyanate and potassium chloride, produce such different results? One important and previously neglected source of ion specificity is the ionic dispersion potential that acts between each ion and the protein. This attractive potential is found to be much stronger for SCN(-) than it is for Cl(-). We present model calculations, performed within a modified ion-specific double-layer theory, that demonstrate the large effect of including these ionic dispersion potentials. The results are consistent with experiments performed on hen egg-white lysozymes and on neutral black lipid membranes. The calculated surface pH and net lysozyme charge depend strongly on the choice of anion. We demonstrate that the lysozyme net charge is larger, and the corresponding Debye length shorter, in a thiocyanate salt solution than in a chloride salt solution. Recent experiments have suggested that pK(a) values of histidines depend on salt concentration and on ionic species. We finally demonstrate that once ionic dispersion potentials are included in the theory these results can quantitatively be reinterpreted in terms of a highly specific surface pH (and a salt-independent pK(a)).

Measurements and Theoretical Interpretation of Points of Zero Charge/Potential of BSA Protein

The points of zero charge/potential of proteins depend not only on pH but also on how they are measured. They depend also on background salt solution type and concentration. The protein isoelectric point (IEP) is determined by electrokinetical measurements, whereas the isoionic point (IIP) is determined by potentiometric titrations. Here we use potentiometric titration and zeta potential (ζ) measurements at different NaCl concentrations to study systematically the effect of ionic strength on the IEP and IIP of bovine serum albumin (BSA) aqueous solutions. It is found that high ionic strengths produce a shift of both points toward lower (IEP) and higher (IIP) pH values. This result was already reported more than 60 years ago. At that time, the only available theory was the purely electrostatic Debye-Hückel theory. It was not able to predict the opposite trends of IIP and IEP with ionic strength increase. Here, we extend that theory to admit both electrostatic and nonelectrostatic (NES) dispersion interactions. The use of a modified Poisson-Boltzmann equation for a simple model system (a charge regulated spherical colloidal particle in NaCl salt solutions), that includes these ion specific interactions, allows us to explain the opposite trends observed for isoelectric point (zero zeta potential) and isoionic point (zero protein charge) of BSA. At higher concentrations, an excess of the anion (with stronger NES interactions than the cation) is adsorbed at the surface due to an attractive ionic NES potential. This makes the potential relatively more negative. Consequently, the IEP is pushed toward lower pH. But the charge regulation condition means that the surface charge becomes relatively more positive as the surface potential becomes more negative. Consequently, the IIP (measuring charge) shifts toward higher pH as concentration increases, in the opposite direction from the IEP (measuring potential).

Why Direct or Reversed Hofmeister Series? Interplay of Hydration, Non-electrostatic Potentials, and Ion Size

A modified Poisson-Boltzmann analysis is made of the double layer interaction between two silica surfaces and two alumina surfaces in chloride electrolyte. The analysis incorporates nonelectrostatic ion-surface dispersion interactions based on ab initio ionic excess polarizabilities with finite ion sizes. A hydration model for the tightly held hydration shell of kosmotropic ions is introduced. A direct Hofmeister series (K > Na > Li) is found at the silica surface while the reversed series (Li > Na > K) is found at alumina, bringing theory in line with experiment for the first time. Calculations with unhydrated ions also suggest that surface-induced dehydration may be occurring at the alumina surface.

Possible origin of the inverse and direct hofmeister series for lysozyme at low and high salt concentrations

Protein solubility studies below the isoelectric point exhibit a direct Hofmeister series at high salt concentrations and an inverse Hofmeister series at low salt concentrations. The efficiencies of different anions measured by salt concentrations needed to effect precipitation at fixed cations are the usual Hofmeister series (Cl(-) > NO(3)(-) > Br(-) > ClO(4)(-) > I(-) > SCN(-)). The sequence is reversed at low concentrations. This has been known for over a century. Reversal of the Hofmeister series is not peculiar to proteins. Its origin poses a key test for any theoretical model. Such specific ion effects in the cloud points of lysozyme suspensions have recently been revisited. Here, a model for lysozymes is considered that takes into account forces acting on ions that are missing from classical theory. It is shown that both direct and reverse Hofmeister effects can be predicted quantitatively. The attractive/repulsive force between two protein molecules was calculated. To do this, a modification of Poisson-Boltzmann theory is used that accounts for the effects of ion polarizabilities and ion sizes obtained from ab initio calculations. At low salt concentrations, the adsorption of the more polarizable anions is enhanced by ion-surface dispersion interactions. The increased adsorption screens the protein surface charge, thus reducing the surface forces to give an inverse Hofmeister series. At high concentrations, enhanced adsorption of the more polarizable counterions (anions) leads to an effective reversal in surface charge. Consequently, an increase in co-ion (cations) adsorption occurs, resulting in an increase in surface forces. It will be demonstrated that among the different contributions determining the predicted specific ion effect the entropic term due to anions is the main responsible for the Hofmeister sequence at low salt concentrations. Conversely, the entropic term due to cations determines the Hofmeister sequence at high salt concentrations. This behavior is a remarkable example of the charge-reversal phenomenon.

Ion Specific Surface Charge Density of SBA-15 Mesoporous Silica

Potentiometric titrations were used to estimate the surface charge density of SBA-15 mesoporous silica in different salt solutions. It was found that surface charge depends both on cation type, following a Hofmeister series (Cs(+) < Guanidinium(+) < K(+) < Na(+) < Li(+)), and on salt concentration (in the range 0.05-1 M). The surface charge series is reproduced by theoretical calculations performed using a modified Poisson-Boltzmann equation that includes ionic dispersion forces with ab initio ion polarizabilities and hydrated ions. The hydration model assigns an explicit hydration shell to kosmotropic (strong hydrated) ions only. The Hofmeister series appears to be due to the combination of ion-surface dispersion interactions and ion hydration.

Hofmeister challenges: Ion binding and charge of the BSA protein as explicit examples

Experiments on bovine serum albumin (BSA) via potentiometric titration (PT) and electrophoretic light scattering (ELS) are used to study specific-ion binding. The effect is appreciable at a physiological concentration of 0.1 M. We found that anions bind to the protein surface at an acidic pH, where the protein carries a positive charge (Z(p) > 0), according to a Hofmeister series (Cl(-) < Br(-) < NO(3)(-) < I(-) < SCN(-)), as well as at the isoionic point (Z(p) = 0). The results obtained require critical interpretation. The measurements performed depend on electrostatic theories that ignore the very specific effects they are supposed to reveal. Notwithstanding this difficulty, we can still infer that different 1:1 sodium salts affect the BSA surface charge/pH curve because anions bind to the BSA surface with an efficiency which follows a Hofmeister series.

Specific ion adsorption and surface forces in colloid science.

Mean-field theories that include nonelectrostatic interactions acting on ions near interfaces have been found to accommodate many experimentally observed ion specific effects. However, it is clear that this approach does not fully account for the liquid molecular structure and hydration effects. This is now improved by using parametrized ionic potentials deduced from recent nonprimitive model molecular dynamics (MD) simulations in a generalized Poisson-Boltzmann equation. We investigate how ion distributions and double layer forces depend on the choice of background salt. There is a strong ion specific double layer force set up due to unequal ion specific short-range potentials acting between ions and surfaces.

Co-Ion and Ion Competition Effects: Ion Distributions Close to a Hydrophobic Solid Surface in Mixed Electrolyte Solutions

We consider within a modified Poisson-Boltzmann theory an electrolyte, with different mixtures of NaCl and NaI, near uncharged and charged solid hydrophobic surfaces. The parametrized potentials of mean force acting on Na+, Cl-, and I- near an uncharged self-assembled monolayer were deduced from molecular simulations with polarizable force fields. We study what happens when the surface presents negative charges. At moderately charged surfaces, we observe strong co-ion adsorption and clear specific ion effects at biological concentrations. At high surface charge densities, the co-ions are pushed away from the interface. We predict that Cl- ions can also be excluded from the surface by increasing the concentration of NaI. This ion competition effect (I- versus Cl-) may be relevant for ion-specific partitioning in multiphase systems where polarizable ions accumulate in phases with large surface areas.

Retardation turns the van der Waals attraction into a Casimir repulsion as close as 3 nm

Casimir forces between surfaces immersed in bromobenzene have recently been measured by Munday et al. [Nature (London) 454, 07610 (2009)]. Attractive Casimir forces were found between gold surfaces ...

The influence of ion binding and ion specific potentials on the double layer pressure between charged bilayers at low salt concentrations

Measurements of surface forces between double-chained cationic bilayers adsorbed onto molecularly smooth mica surfaces across different millimolar salt solutions have revealed a large degree of ion specificity [Pashley et al., J. Phys. Chem. 90, 1637 (1986)]. This has been interpreted in terms of highly specific anion binding to the adsorbed bilayers. We show here that inclusion in the double layer theory of nonspecific ion binding and ion specific nonelectrostatic potentials acting between ions and the two surfaces can account for the phenomenon. It also gives the right Hofmeister series for the double layer pressure.