Droplets of Life

Membrane-Less Organelles, Biomolecular Condensates, and Biological Liquid-Liquid Phase Separation

1st Edition - November 9, 2022
Imprint: Academic Press
Editor: Vladimir N Uversky
Language: English
Paperback ISBN:
9 7 8 - 0 - 1 2 - 8 2 3 9 6 7 - 4
eBook ISBN:
9 7 8 - 0 - 1 2 - 8 2 4 1 7 5 - 2

Droplets of Life: Membrane-Less Organelles, Biomolecular Condensates, and Biological Liquid–Liquid Phase Separation provides foundational information on the biophysics, biogenesi… Read more

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Droplets of Life: Membrane-Less Organelles, Biomolecular Condensates, and Biological Liquid–Liquid Phase Separation provides foundational information on the biophysics, biogenesis, structure, functions, and roles of membrane-less organelles. The study of liquid–liquid phase separation has attracted a lot of attention from disciplines such as cell biology, biophysics, biochemistry, and others trying to understand how, why, and what roles these condensates play in homeostasis and disease states in living organisms. This book's editor recruited a group of international experts to provide a current and authoritative overview of all aspects associated with this exciting area.

Sections introduce membrane-less organelles (MLOs) and biomolecular condensates; MLOs in different sizes, shapes, and composition; and the formation of MLOs due to phase separation and how it can tune reactions, organize the intracellular environment, and provide a role in cellular fitness.

Cover image
Title page
Table of Contents
Copyright
Contributors
Part I. Introduction to membrane-less organelles and biomolecular condensates
Chapter 1. Biophysical principles of liquid–liquid phase separation
Introduction
Aqueous solution of nonionic polymers
Types of two-phase systems in water
Phase diagrams
Properties of coexisting phases and solute partitioning in aqueous two-phase system
Existing approaches to description of phase diagrams of ATPS and likely mechanism of liquid–liquid phase separation
Theoretical treatments based on virial expansion model
Theoretical treatment based on the excluded volume principle
Chapter 2. Major structural features of membrane-less organelles
Introduction
Proteins
Nucleic acids
Outlook and future studies
Chapter 3. Biochemical and structural biology aspects of liquid–liquid phase separation: protein side of liquid–liquid phase separation, membrane-less organelles, and biomolecular condensates
Introduction
Liquid–liquid phase separation and membrane-less organelles
Intrinsically disordered proteins
Liquid–liquid phase separation, intrinsically disordered proteins, and membrane-less organelles
Intrinsically disordered proteins in liquid–liquid phase separation: some general considerations
Concluding remarks
Chapter 4. Biochemical and structural biology aspects of liquid–liquid phase separation: an interplay between proteins and RNA
RNA plays a critical role in the formation and regulation of biomolecular condensates
RNA buffers condensate formation
RNA seeds droplet formation
RNA–protein interactions define condensate properties and spatial organization
RNA self-assembly promotes phase separation
RNA–protein interactions underlying phase separation
Structural biology of RNA-binding domains
RGG/RG motif
RNA recognition motif
K homology domain
Zinc finger
Domain cooperativity
Posttranslational modifications
RNA protein dynamics correlate to droplet properties
Disease connection
Conclusion
Chapter 5. Liquid–liquid phase separation and biomolecular condensates in cell quiescence
Introduction
Cell quiescence, biomolecular condensates, and liquid–liquid phase separation
Conclusions
Chapter 6. Multiphase complex droplets
Introduction
Phase behavior of multicomponent mixtures
Phase coexistence and kinetically trapped states
Hierarchically structured condensates in cell biology
Multiphase model systems
Physical basis of multiphase coexistence
Functional implications of multiphase droplets
Chapter 7. Techniques for the detection and analysis of LLPS and MLOs
Introduction
Visualization-based approaches of the liquid–liquid phase separation characterization
Methods for the characterization of the biomolecular condensate properties
Methods for liquid–liquid phase separation prediction
Peculiarities of the conducting membrane-less organelle analysis
Chapter 8. Guidelines for experimental characterization of liquid–liquid phase separation in vitro
An introduction to liquid–liquid phase separation
In silico studies
Liquid–liquid phase separation databases
In vitro liquid–liquid phase separation assays
Constructing a phase diagram
Thermoresponsive phase behavior
Characterization of conformational disorder, distribution, dynamics, and heterogeneity
Material properties of condensates
Future directions
Chapter 9. Liquid–liquid phase separation at the origins of life
Introduction
Products of liquid–liquid phase separation
Ingredients for liquid–liquid phase separation
Environment of membrane-less organelles at the origins of life
Advantages of membrane-less organelles at the origins of life
Protocells
RNA, DNA, and nucleotides
Amino acids, peptides, and proteins
Lipids
Wet–dry cycles
Are membrane-less organelles always liquid?
A prebiotic ecosystem
Conclusion
Part II. Biology of membrane-less organelle
Chapter 10. Known types of membrane-less organelles and biomolecular condensates
Introduction
Cytoplasmic membrane-less organelles
Metabolic condensates
Germ cell membrane-less organelles
Nuclear membrane-less organelles
Mitochondrial and chloroplast membrane-less organelles
Bacterial membrane-less organelles and condensates
Conclusions
Chapter 11. Active regulation mechanisms of LLPS and MLOs biogenesis
Phase separation is controlled by changes in the local concentration of biomolecules
Active transport by molecular motors governs the assembly and disassembly of membrane-less organelles
Biochemical modifications of RNA influence liquid–liquid phase separation
Posttranslational modifications of proteins regulate liquid–liquid phase separation
Membrane-less organelle dynamics and cellular physiology
Chapter 12. Interactions and interplay of MLOs with classical membrane-bound organelles
Compartmentalization of cells
Membrane-bound organelles and their functions
Membrane-less organelles
Comparison of membrane-bound organelles and membrane-less organelles
Interaction of membrane-bound organelles with membrane-less organelles
Membrane-bound organelles in diseases
Conclusions
Chapter 13. Intrinsically disordered regions: a platform for regulated assembly of biomolecular condensates
Introduction
P-bodies
Germ granules
Transport granules
Whi3 granules
TIS granules
Pyrenoid
Stress-induced cytoplasmic condensates
Pathological condensates
Conclusions
Outlook
Chapter 14. MLOs and control of metabolic pathways
Membrane-less organelles in metabolism
Enzymatic reactions of in vivo metabolism
Molecular packing of enzymes and substrates in a restricted space facilitates efficient enzymatic reactions in cells
How is clustering of metabolic enzymes, substrates, and intermediates organized and controlled in cells?
A model for metabolic MLOs: mitochondrial droplets control cardiolipin (CL) metabolism
How can Mieap drive formation of mitochondrial MLOs and enable sequential enzymatic reactions?
Separation of enzymes and substrates into distinct membrane-less compartments enhances enzymatic reactions
How can Mieap drive sequential enzymatic reactions in multiphase droplets?
Perspective: What is the real picture of metabolic MLOs under physiological conditions?
Chapter 15. LLPS and regulation of transmembrane signaling
Introduction
Membrane rafts as a two-dimensional liquid–liquid phase separation
Membrane rafts in metabolic regulation and cell signaling
On the possibility of signal transmission through the phase transition wave
Conclusions
Chapter 16. Phase separation in chromatin-based intranuclear processes
Introduction
Nucleosomes and chromatin fibers
Transcription-related hubs
DNA repair hubs
Heterochromatin and euchromatin domains
Higher-order chromatin structures
Linking genomic plasticity with cellular robustness
Mechanisms of phase separation in chromatin: LLPS, PPPS, or others?
Conclusions
Chapter 17. MLOstasis: liquid–liquid phase separation and biomolecular condensates in cell competition, fitness, and aging
Introduction
MLOstasis and cell fitness
Liquid–liquid phase separation in cell competition
Liquid–liquid phase separation, cellular aging, and cellular senescence
Conclusions
Chapter 18. Stress, membraneless organelles, and liquid–liquid phase separation
Introduction
Protein sensitivity to environmental changes, liquid-liquid phase separation, and membraneless organelle formation
Membraneless organelle contents and characteristics
Membraneless organelles in the stress response
Liquid–liquid phase separation and the stress response
Interaction among membraneless organelles
Are membraneless organelle adaptive?
Stress, membraneless organelles, disease, and the future of biomedicine
Chapter 19. Roles of phase separation and condensates in autophagy
Introduction
Regulation of autophagy initiation by liquid–liquid phase separation
Role of liquid–liquid phase separation in selective autophagy
p62 bodies
Stress granules
PGL granules
The Ape1 complex
Ede1-dependent endocytic protein deposits
Common principles of the selective autophagy of biomolecular condensates
Chapter 20. Liquid–liquid phase in anhydrobiosis
Desiccation tolerance, liquid–liquid phase separation, and biomolecular condensates
Protein stabilization: the “ark” hypothesis
Cell stabilization—viscosity-based protection mechanisms
Conclusions
Chapter 21. Plant biomolecular condensates
Introduction
Biomolecular condensates and plant developmental processes
Biomolecular condensates and plant environmental responses
Future perspectives
Chapter 22. Droplets of life: role of phase separation in virus replication and compartmentalization
Introduction to liquid–liquid phase separation
Liquid–liquid phase separation by viral proteins
Implications of LLPS and MLOs for drug design
Conclusions
Part III. Pathological roles of LLPS
Chapter 23. Liquid–liquid phase separation in neurodegenerative diseases
Protein aggregation and neurodegenerative diseases
Liquid–liquid phase separation of proteins involved in neurodegenerative diseases
Chapter 24. Emerging roles of liquid–liquid phase separation and membraneless organelles in cancer progression
Introduction
Cancer pathways that involve liquid–liquid phase separation
Toward liquid–liquid phase separation–based cancer therapeutics
Chapter 25. Liquid–liquid phase separation, membrane-less organelles, and biomolecular condensates in cardiovascular disease
Introduction
Protein intrinsic disorder and cardiovascular disease
Liquid–liquid phase separation in cardiovascular disease
Concluding remarks
Chapter 26. Phase separation and infectious diseases
Introduction
Infectious diseases, antiinfection immune response, and phase separation
Concluding remarks
Index

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