Aggregation or phase separation can be induced in highly charged proteins by small charged biomolecules

Protein phase separation in biological systems has captured the attention of scientists in the last decade; however, the main mechanism underlying protein phase separation in cells remains unclear. Biologists, physicists, and chemists have all tried to understand this important biological phenomenon, each using their own unique techniques and language. Each subject has its advantages in explaining protein phase separation; however, in this study, we find that the chemical language of molecular structure is the key to explaining the mechanism underlying protein phase separation. Using fluroescence microscopy and molecular dynamics, this study identifies small multivalently charged biomolecules, such as nucleoside triphosphate (negatively charged) and polyamine (positively charged), as important drivers of phase separation of highly charged proteins in cells.