Staying Together: Protein Molecules in Mesoscopic Clusters.

Collective behavior of protein molecules in solutions is critically important for understanding their biological functions, as well as for efficient control of various technological processes. A number of recent experimental studies have observed the formation of various clusters in protein solutions in different systems (1–5). While the existence of small molecular complexes in solutions is a common phenomenon, a surprising thing in protein solutions is a variety and complexity of such aggregates. At least three different classes of protein clusters, depending on their sizes and volume fractions, have been reported in experiments (6). But the most intriguing of them are mesoscopic protein clusters, for which the mechanisms of assembly are still not well understood (4,6,7). These mesoscopic clusters are also very important for clarifying many phenomena in chemistry, biology, and medicine because they frequently serve as nucleation sites for the formation of ordered and disordered protein solid aggregates such as protein crystals, sickle cell hemoglobin polymers, and amyloid fibrils (8,9). Mesoscopic protein clusters are relatively large: typically, the number of protein molecules in them is ~10– 10, and their diameters vary from 100 to several hundreds of nanometers (4,7,8). At the same time, the number of mesoscopic clusters is relatively small and they occupy a tiny fraction