Synchronous assembly of peptide anisosome

Biomolecular condensates, formed by liquid-liquid phase separation (LLPS) of proteins or the complex of protein and nucleic acids, play key roles in regulating physiological events in biological system. However, the formation of mono-component yet inhomogeneous condensates is limited, and the underlying mechanism remains unclear. Here, we report the symmetrical core-shell structural biomolecular condensates formed through the LLPS by programming a tetra-peptide library. Mechanistic studies reveal that the tryptophan (W) is critical for the formation of core-shell structure because of its stronger homotypical {pi}-{pi} interaction compared with other amino acids, which endow us to modulate the droplets from core-shell to homogeneous structures by encoding the amino acid composition. Using molecular dynamics (MD) simulation and molecular engineering, we find that the inner core of LLPS is composed of dynamic and reversible fibers surrounded by liquid-like shells, resulting in a stable core-shell LLPS. Furthermore, we could control the multiphasic droplet formation by an intrinsic redox reaction or post-translational modification of peptide through phosphorylation, which facilitates the rational design of synthetic LLPS with various applications on demand.