Liquid-Liquid Phase Separation in Oligomeric Peptide Solutions

Oligomeric peptides exist widely in living organisms and play a role in a broad range of biological functions. We report the first observation of liquid-liquid phase separation (LLPS) in peptide solutions, in particular, solutions of peptides consisting of noncovalent oligomers. We determined the binary phase boundary of the oligomeric peptide solution and compared the result to the well-established phase diagram of globular proteins. We also provide simple theoretical interpretations of the similarities and differences between the phase diagrams of peptides and proteins. Finally, by tuning inter-oligomer interactions using a crowding agent, we demonstrated that LLPS is a universal phenomenon that can be observed under different solution conditions for a variety of peptides.