Effect of the surface charge distribution on the fluid phase behavior of charged colloids and proteins

Abstract

A generic but simple model is presented to evaluate the effect of the heterogeneous surface charge distribution of proteins and zwitterionic nanoparticles on their thermodynamic phase behavior. By considering surface charges as continuous “patches”, the rich set of surface patterns that is embedded in proteins and charged patchy particles can readily be described. This model is used to study the fluid phase separation of charged particles where the screening length is of the same order of magnitude as the particle size. In particular, two types of charged particles are studied: dipolar fluids and protein-like fluids. The former represents the simplest case of zwitterionic particles, whose charge distribution can be described by their dipole moment. The latter system corresponds to molecules/particles with complex surface charge arrangements such as those found in biomolecules. The results for both systems suggest a relation between the critical region, the strength of the interparticle interactions, and the arrangement of charged patches, where the critical temperature is strongly correlated to the magnitude of the dipole moment. Additionally, competition between attractive and repulsive charge–charge interactions seems to be related to the formation of fluctuating clusters in the dilute phase of dipolar fluids, as well as to the broadening of the binodal curve in protein-like fluids. Finally, a variety of self-assembled architectures are detected for dipolar fluids upon small changes to the charge distribution, providing the groundwork for studying the self-assembly of charged patchy particles.

Electrostatically Mediated Protein-Protein Interactions for Monoclonal Antibodies: A Combined Experimental and Coarse-Grained Molecular Modeling Approach

“…Unlike MAb A, MAb B exhibits electrostatic attractions at intermediate TIS values, which are apparent because decreasing ionic strength results in increasing attractive PPI (i.e., increasingly negative values of k D ) in some cases, as expected if there are strong dipole or higher multipole interactions due to anisotropic surface charge distributions. 10,[45][46][47][48] The relative importance of anisotropic surface charge distributions is expected to depend on the net charge of the protein and should contribute more to the net PPI when the protein net charge is near zero. 7,42 For MAb B, pH 8 is relatively far from the isoelectric point (pI~5-6), and the profile of k D versus TIS is similar to that for MAb A, where electrostatic attractions were negligible.…”

Limiting the valence: advancements and new perspectives on patchy colloids, soft functionalized nanoparticles and biomolecules

“…102 Janus-like dipolar particles and protein-like units have also been modeled to understand how the charge distribution affects the properties of the fluid phase with a particular focus on gas-liquid phase separation. 103 Finally, a highly sophisticated model for particles with icosahedral, octahedral, and tetrahedral charge decorations has been put forward to describe the effective interactions between viral capsids. 104 Within this broad class of systems, we focus in the following on the results accumulated so far for the most studied IPC systems.…”

“…At physiological pH values, this results in a heterogeneous surface charge, with the range of the electrostatic interactions being set by the screening provided by ions in solution. 103,113,114 The effect of heterogeneous surface charges and ion condensation on proteinprotein interactions has recently been described in ref. 115 by an appropriately developed multipolar coarse-grained model.…”

“…As pointed out in Section 2.1, this class of proteins is related to charged patchy colloids, and several models are being developed in this respect. 100,103 The appropriate modeling of directional interactions caused by charge inhomogeneities can be challenging, in particular with respect to specific ion effects: for instance, by forming salt bridges, multivalent ions have very drastic effects on the effective interactions between proteins in solution to the point of rendering directional charge repulsions attractive. 116 More refined models which take into account electric multipoles as well as the distribution of charged, neutral and hydrophobic residues have been developed.…”

Surface heterogeneity affects percolation and gelation of colloids: dynamic simulations with random patchy spheres

“…Patchy particles are compared with uniform particles to elucidate the effect of surface heterogeneity on percolation and gelation. Recent work by Blanco and Shen (2016), 70 has analyzed spherical particles with a small number of symmetrically positioned patches reflecting different dipolar and quadrupolar charge distributions that could be correlated with phase behavior and percolation.…”