Understanding inverted solubility through specialized patchy particle models

The high specificity and anisotropy of protein-protein interactions give rise to remarkably rich phase and assembly behaviors. A thorough understanding of these interactions is notably key to forming crystals for protein structure determination. Despite the inherent complexity of these biomolecular systems, coarse-grained patchy models can be used to elucidate the physico-chemical processes that govern protein self-assembly. Here, we consider crystal formation in certain mutants of human γD-crystallin, which remarkably form assemblies that become less soluble as temperature increases. We find that using a minimal patchy model with temperature-deactivated patches recapitulates this inverted solubility trend and provides microscopic insights into the origin of this unusual behavior. This finding provides physical constraints for the observation of retrograde solubility in soft matter more generally.