Peptide self-assembly through liquid-liquid phase separation

Summary

Peptide self-assembly provides an innovative strategy for not only establishing an ideal research model to understand life phenomena but also for constructing sophisticated functional materials toward advanced frontier nanotechnology. Increasing evidence has demonstrated that peptides undergo self-assembly through liquid-liquid phase separation (LLPS), which is in contrast to the classical self-assembly model via monomer-by-monomer addition. The general principle underlying LLPS-mediated self-assembly is critical to the design and exploration of peptide-based supramolecular materials but remains largely unknown. Therefore, this review focuses on the latest studies of LLPS-mediated peptide self-assembly and explores the thermodynamic and kinetic mechanisms responsible for this non-classical pathway. Based on current understanding, we propose a basic principle of LLPS-mediated multistep self-assembly, which is distinct from the classical single-step self-assembly based on monomer-by-monomer addition. Finally, we evaluate the fundamental hurdles and provide future direction focusing on the mechanistic comprehension and diverse application of LLPS-mediated biomolecular self-assembly in living systems.