Liquid-Liquid Phase Separation of Peptide-Based Biomacromolecules: Mechanisms, Responsive Factors, and Biomedical...

Area of Science:

• Biochemistry and Molecular Biology
• Materials Science
• Biotechnology

Background:

• Liquid-liquid phase separation (LLPS) is a fundamental process driving biomolecular coacervate formation.
• Coacervates are vital for cellular organization and implicated in various disease developments.
• Understanding LLPS mechanisms is key to harnessing coacervates for novel applications.

Purpose of the Study:

• To systematically review the LLPS properties of proteins and peptides.
• To elucidate coacervate classification and sequence-based molecular design principles.
• To bridge fundamental coacervate characteristics with their biomedical applications.

Main Methods:

• Systematic summarization of LLPS properties for proteins and peptides.
• Analysis of coacervate classification and sequence-based design principles.
• Evaluation of kinetic aspects (nucleation, self-assembly) and environmental factor regulation (pH, ionic strength, redox potential, enzymes).

Main Results:

• Synergistic intermolecular forces are critical for governing phase separation.
• The coalescence process involves nucleation barriers and subsequent self-assembly.
• Coacervate material properties are precisely regulated by environmental factors.
• Protein/peptide coacervates exhibit reversible dissociation, tunable phase transitions, and biocompatibility.

Conclusions:

• Protein and peptide coacervates are versatile dynamic systems with significant potential.
• Their tunable properties enable development as advanced biomaterials.
• These materials show promise for applications in bioadhesives, microreactors, drug delivery, and optical signals.
• Bridging fundamental science to clinical translation is highlighted for future research and development.