Title:Control of Aggregation, Coaggregation, and Liquid Droplet of Proteins Using Small Additives
Volume: 19
Issue: 12
Author(s): Kazuki Iwashita, Masahiro Mimura and Kentaro Shiraki*
Affiliation:
- Faculty of Pure and Applied Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8573,Japan
Keywords:
Aggregation, coaggregation, liquid-liquid phase separation, droplet, additive, protein.
Abstract: This review article presents the concepts of aggregates, coaggregates, and a liquid droplet of
proteins and compares the concentrated states in the presence of small additives to control their formation
and dissociation. The aggregates composed of single protein molecules result mainly from hydrophobic
interactions between unfolded protein molecules. Thus, the aggregation of protein can be effectively
suppressed by small additives that increase the solubility of hydrophobic solutes, typically arginine
(Arg) and chaotropes. In contrast, coaggregation that is composed of two or more types of proteins
results from both hydrophobic and attractive electrostatic interactions between even partially unfolded
protein molecules. Accordingly, coaggregation is more controllable than simple aggregation using
various types of small additives, such as ions and osmolytes, as well as Arg and chaotropes. The liquid
droplets of proteins observed in living cells and a protein-polyelectrolyte complex (PPC) undergo
liquid-liquid phase separation driven only by electrostatic interactions. Thus, the liquid droplets and
PPCs are redissolved when the concentration of ions is increased. The properties of electrostatic or hydrophobic
interactions, solid-like or liquid-like states, and apparently spherical and amorphous structures
are simple but valuable criteria that can be used to control protein aggregation and condensation
using small additives.
