Regulation of Peptide Liquid–Liquid Phase Separation by Aromatic Amino Acid Composition

Membraneless organelles are cellular biomolecular condensates that are formed by liquid–liquid phase separation (LLPS) of proteins and nucleic acids. LLPS is driven by multiple weak attractive forces, including intermolecular interactions mediated by aromatic amino acids. Considering the contribution of π-electron bearing side chains to protein-RNA LLPS, systematically study sought to how the composition of aromatic amino acids affects the formation of heterotypic condensates and their physical properties. For this, a library of minimalistic peptide building blocks is designed containing varying number and compositions of aromatic amino acids. It is shown that the number of aromatics in the peptide sequence affect LLPS propensity, material properties and (bio)chemical stability of peptide/RNA heterotypic condensates. The findings shed light on the contribution of aromatics’ composition to the formation of heterotypic condensates. These insights can be applied for regulation of condensate material properties and improvement of their (bio)chemical stability, for various biomedical and biotechnological applications.