Dear Colleagues,

In the past few years, liquid–liquid phase separation (LLPS) has emerged as a universal language in biomolecular signaling, hub interactions, intracellular compartmentalization, and in pathological dysfunction in the cell. LLPS is a spontaneous phase transition that occurs as a result of the thermodynamic instability of a uniformly mixed state. LLPS is largely driven by proteins with intrinsically disordered regions (IDRs) of promiscuous binding behavior. The LLPS-mediated dynamic clustering of cellular factors, enzymes, and nucleic acids has been linked to almost all aspects of RNA metabolism, gene activation and repression, regulation of transcriptional and translational programming, stress modulation, and other cellular functions. In parallel, aberrant phase transition (e.g., liquid-to-solid phase transition) has been observed in multiple neurological disease-linked systems and age-onset disorders.

Understanding the regulation, function, and pathological consequences of LLPS in biological systems is a key topic of interest in this field. The IDRs that mediate phase separation have signature sequences of low complexity with distinct sequence composition and patterning. They often harbor sites for post-translational modifications (PTMs), which is thought to confer the regulation of LLPS. Besides PTM, nucleic acids are also known to regulate phase separation and physical properties of biomolecular condensates.

The fundamental physics behind LLPS has been studied for decades in the context of synthetic polymers, which provides an essential bedrock to understand LLPS in biological systems. Recent years also saw the discovery of new physical principles to model LLPS and its active regulation in the assembly of biological macromolecules. In addition to understanding the phase behavior, new biophysical tools are being developed to study the material states and compositional control of the condensed phase which are intricately linked to its physiological function. The diverse spectrum of phase-separating IDRs harbors myriad physical and chemical interactions, which is translated into different pathways of creating distinct physical and functional variants of biomolecular condensates. Understanding the molecular rules that govern the phase separation in biological systems has broader implications, such as new design principles of soft bio-inspired materials.

This Special Issue of Biomolecules is focused on highlighting the roles of phase separation in biological systems. This involves, but is not limited to, the exploration of old and new biological macromolecules that undergo phase separation in vitro and in vivo, the regulation and function of biological condensates, the emergent structure and dynamics of phase-separated bodies, engineering de novo biomolecular condensates, and the quantitative modeling of phase behavior in biological systems.

Prof. Priya R. Banerjee
Guest Editor

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• Biomolecular condensates
• Membrane-less organelles
• Self-assembly of proteins and nucleic acids
• Protein droplets
• Phase transition of biopolymers
• Mesoscale biology
• Amyloid fibrillation
• RNA-binding proteins
• Low-complexity sequences
• Intrinsically disordered proteins