Physics of protein-polyelectrolyte complexes

A mixture of proteins and polyelectrolytes are widely used in applications such as food systems, biosensors, protein purification, drug delivery. Experiments have demonstrated that the structures and phase behavior of protein-polyelectrolyte mixture can be dependent on a variety of factors, including the physical and chemical characteristics of proteins, polyelectrolytes, properties of solution, and temperature. Despite extensive experimental studies, there is still a lack of a theoretical framework to understand the fundamental physics which is capable of capturing the complexities of the phase behavior of protein-polyelectrolyte mixtures and be able to predict the impact of the component properties on the structure of these mixtures. Motivated by the lack of studies, in this thesis, we have built a single chain in mean-field based coarse-grained multibody simulation framework to study the phase behavior of protein and polyelectrolyte complexes. We have explored the influence of features such as the dielectric difference between the protein and the solvent, charge distribution of proteins, and the solution pH. Our results demonstrate that the pattern of charge heterogeneities can exert a significant influence on the resulting characteristics of the aggregates, in some cases leading to a transformation from polymer-bridged complexes to direct protein aggregates driven by attraction between oppositely charged patches. Later, we appended the framework to capture the influence of variable charge on proteins and polyelectrolytes due to variation in their dissociation characteristics in the presence of other charged species and properties of the solution. We probe the influence of charge patches on the bridging probabilities near the protein isoelectric points and in regimes in which the net charge of the protein is the same sign as that of the polyelectrolytes. Our results demonstrate that in the presence of dissociable polyelectrolytes, the probability of bridging of proteins capable of charge regulation is enhanced relative to proteins which are completely dissociated. For homogeneously charged proteins and/or proteins with weak charge heterogeneities, partially dissociated polyelectrolytes are seen to exhibit enhanced bridging characteristics compared to completely dissociated polyelectrolytes. In contrast, for proteins exhibiting strong charge heterogeneities, dissociable polyelectrolytes are seen to exhibit weaker bridging compared to completely dissociated polyelectrolytes. Upon including the feature of dielectric contrast in the model, our results demonstrated that the proteins experienced an increased repulsion with a lowering of the ratio of protein to the solvent dielectric constant. However, the influence of dielectric contrast diminishes with an increase in the particle volume fraction and/or its charge. In the presence of neutral polymers, similar effects manifest, but with the additional physics arising from the fact that the polymer-induced interactions are influenced by the dielectric contrast of the protein and solvent. Finally, we designed a framework to capture the phase diagram of the protein