Liquid–Liquid Phase Separation of Peptides: A Molecular Foundation for Next-Generation Biomaterials

Abstract

Liquid–liquid phase separation (LLPS) is a key mechanism for organizing membraneless cellular compartments, influencing processes like stress response, signaling, and gene regulation. While intrinsically disordered proteins (IDPs) and their regions (IDRs) drive LLPS through weak, multivalent interactions, the complexity of full-length proteins limits systematic design and understanding of phase separation. Peptides, as simpler modular units, offer precise control over sequence composition and provide a scalable platform for studying LLPS. Recent advancements demonstrate that peptide condensates reveal fundamental phase separation rules and enable applications such as artificial cells and drug delivery systems. This Perspective highlights recent progress in peptide LLPS, focusing on sequence design, structural characterization, and emerging applications, and discusses challenges and future directions for broader applications.