Functional Implications of Intracellular Phase Transitions

Abstract

Intracellular environments are heterogeneous milieus comprised of macromolecules, osmolytes, and a range of assemblies that include membrane-bound organelles and membraneless biomolecular condensates. The latter are nonstoichiometric assemblies of protein and RNA molecules. They represent distinct phases and form via intracellular phase transitions. Here, we present insights from recent studies and provide a perspective on how phase transitions that lead to biomolecular condensates might contribute to cellular functions.

Composition dependent phase separation underlies directional flux through the nucleolus

“…Biomolecular interactions, particularly homotypic interactions mediated by self-associating intrinsically disordered protein regions (IDRs), are thought to underlie the thermodynamic driving forces for LLPS, forming condensates that can facilitate the assembly and processing of biochemically active complexes, such as ribosomal subunits within the nucleolus. Simplified model systems 3-6 have led to the concept that a single fixed saturation concentration (C sat ) is a defining feature of endogenous LLPS 7-9 , and has been suggested as a mechanism for intracellular concentration buffering 2,7,8,10 . However, the assumption of a fixed C sat remains largely untested within living cells, where the richly multicomponent nature of condensates could complicate this simple picture.…”

Dynamic Synthetic Cells Based on Liquid–Liquid Phase Separation

“…[44] Recent studies have also aimed at describing thep hysics underlying phases eparationi nl ivingc ells by adaptingtheoriesusedtodescribe LLPSinsynthetic polymers. [45] Living cells exploit membrane-free compartmentalisation for av ariety of cellular functions, [46] including spatiotemporal regulation of biochemical reactions, [4,47] contents organisation during division [48] and signal amplification, integration or attenuation through passiven oise filtration in order only to detect and to respondt or elevant signals. These properties are based on either passiveo ra ctive processes that endow the droplets with specific material properties, ensure selective partitioning of biomolecules or prevent aging and fusion.…”

“…These properties are based on either passiveo ra ctive processes that endow the droplets with specific material properties, ensure selective partitioning of biomolecules or prevent aging and fusion. [45] Living cells exploit membrane-free compartmentalisation for av ariety of cellular functions, [46] including spatiotemporal regulation of biochemical reactions, [4,47] contents organisation during division [48] and signal amplification, integration or attenuation through passiven oise filtration in order only to detect and to respondt or elevant signals. [49] Changes in the material properties of liquid-like droplets have further been relatedt od iseases, due to, for example, arrested dynamics (gelation) and protein fibril formation.…”

Prediction of liquid-liquid phase separation proteins using machine learning

“…Proteins involved in LLPS can be categorized as scaffold proteins (scaffolds) and client proteins (clients) [11,12]. Scaffolds are defined as the drivers of LLPS while clients have been discovered to co-occurrence with scaffolds in experimental conditions, but lack of evidence of whether they can undergo LLPS or not independently.…”

“…Fundamentally, the reversible multi-valent interactions between bio-molecules drive LLPS process, which can be occurred between multiple folded domains or be mediated by intrinsically disordered proteins (IDPs). Generally, phase separation related proteins can be categorized as scaffolds which drive LLPS, and clients, which participate into the condensates formed by scaffolds [11,12]. Although tremendous progress has been made in understanding protein LLPS, the knowledge of prevalence and distribution of phase separation proteins (PSPs) is still lacking.…”