Thermodynamically Driven Assemblies and Liquid-liquid Phase Separations in Biology

Abstract

The sustenance of life depends on the high degree of organization that prevails through different levels of living organisms, from subcellular structures such as biomolecular complexes and organelles to tissues and organs. The physical origin of such organization is not fully understood, and even though it is clear that cells and organisms cannot maintain their integrity without consuming energy, there is growing evidence that individual assembly processes can be thermodynamically driven and occur spontaneously due to changes in thermodynamic variables such as intermolecular interactions and concentration. Understanding the phase separation \emph{in vivo} requires a multidisciplinary approach, integrating the theory and physics of phase separation with experimental and computational techniques. This paper aims at providing a brief overview of the physics of phase separation and its biological implications, with a particular focus on the assembly of membraneless organelles. We discuss the underlying physical principles of phase separation from its thermodynamics to its kinetics. We also overview the wide range of methods utilized for experimental verification and characterization of phase separation of membraneless organelles, as well as the utility of molecular simulations rooted in thermodynamics and statistical physics in understanding the governing principles of thermodynamically driven biological self-assembly processes.

23 pages, 6 figures

References in corpus (39)

• Escaping free-energy minima
• Well-Tempered Metadynamics: A Smoothly Converging and Tunable Free-Energy Method
• An efficient, multiple range random walk algorithm to calculate the density of states
• Parallel Tempering: Theory, Applications, and New Perspectives
• Phase diagram of patchy colloids: towards empty liquids
• A Novel Path Sampling Method for the Calculation of Rate Constants
• Growth and Division of Active Droplets: A Model for Protocells
• Sampling rare switching events in biochemical networks
• Simulating rare events in equilibrium or non-equilibrium stochastic systems
• Phase separation and single-chain compactness of charged disordered proteins are strongly correlated
• Elaborating Transition Interface Sampling Methods
• Sequence-specific polyampholyte phase separation in membraneless organelles
• Direct Calculation of Ice Homogeneous Nucleation Rate for a Molecular Model of Water
• On the Wang-Landau Method for Off-Lattice Simulations in the "Uniform" Ensemble
• Controlling crystallization and its absence: Proteins, colloids and patchy models
• Liquids more stable than crystals
• Phase transitions in biological systems with many components
• Phase behavior and morphology of multicomponent liquid mixtures
• Evaporation Rate of Water in Hydrophobic Confinement
• Extended surfaces modulate and can catalyze hydrophobic effects
• Random-phase-approximation theory for sequence-dependent, biologically functional liquid-liquid phase separation of intrinsically disordered proteins
• Charge Pattern Matching as a "Fuzzy" Mode of Molecular Recognition for the Functional Phase Separations of Intrinsically Disordered Proteins
• A simple patchy colloid model for the phase behavior of lysozyme dispersions
• Coarse-Grained Residue-Based Models of Disordered Protein Condensates: Utility and Limitations of Simple Charge Pattern Parameters
• Ice Nucleation on Carbon Surface Supports the Classical Theory for Heterogeneous Nucleation
• A Lattice Model of Charge-Pattern-Dependent Polyampholyte Phase Separation
• Pathways to dewetting in hydrophobic confinement
• Instabilities in complex mixtures with a large number of components
• Phase Diagram of Hard Tetrahedra
• Surface Induced Crystallization in Supercooled Tetrahedral Liquids
• Suppression of Sub-surface Freezing in Free-Standing Thin Films of a Coarse-grained Model of Water
• Degenerate Quasicrystal of Hard Triangular Bipyramids
• Stress granule formation via ATP depletion-triggered phase separation
• Forward-Flux Sampling with Jumpy Order Parameters
• Droplet Ripening in Concentration Gradients
• Computational investigation of structure, dynamics and nucleation kinetics of a family of modified Stillinger-Weber model fluids in bulk and free-standing thin films
• Diffusive dynamics of contact formation in disordered polypeptides
• Perspective: Surface Freezing in Water: A Nexus of Experiments and Simulations
• Calibrated Langevin dynamics simulations of intrinsically disordered proteins

Cited by in corpus (5)

• Studying Rare Events using Forward-Flux Sampling: Recent Breakthroughs and Future Outlook
• How to Quantify and Avoid Finite Size Effects in Computational Studies of Crystal Nucleation: The Case of Heterogeneous Ice Nucleation
• Phase separation and protein partitioning in compartmentalized cell-free expression reactions
• Universal limiting behaviour of reaction-diffusion systems with conservation laws
• The impact of pressure on the critical miscibility of nitro compounds and n-alkanes mixtures