Equilibrium cluster formation in concentrated protein solutions and colloids

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Abstract
Controlling interparticle interactions, aggregation and cluster formation is of central importance in a number of areas, ranging from cluster formation in various disease processes to protein crystallography and the production of photonic crystals. Recent developments in the description of the interaction of colloidal particles with short-range attractive potentials have led to interesting findings including metastable liquid–liquid phase separation and the formation of dynamically arrested states (such as the existence of attractive and repulsive glasses, and transient gels)1,2,3,4,5,6,7. The emerging glass paradigm has been successfully applied to complex soft-matter systems, such as colloid–polymer systems8 and concentrated protein solutions9. However, intriguing problems like the frequent occurrence of cluster phases remain10,11,12,13. Here we report small-angle scattering and confocal microscopy investigations of two model systems: protein solutions and colloid–polymer mixtures. We demonstrate that in both systems, a combination of short-range attraction and long-range repulsion results in the formation of small equilibrium clusters. We discuss the relevance of this finding for nucleation processes during protein crystallization, protein or DNA self-assembly and the previously observed formation of cluster and gel phases in colloidal suspensions12,13,14,15,16,17.