Article
Multidisciplinary Sciences
Avigail Baruch Leshem, Sian Sloan-Dennison, Tlalit Massarano, Shavit Ben-David, Duncan Graham, Karen Faulds, Hugo E. Gottlieb, Jordan H. Chill, Ayala Lampel
Summary: Inspired by the role of intracellular liquid-liquid phase separation (LLPS) in the formation of membraneless organelles, researchers have developed dynamic compartments formed by LLPS of intrinsically disordered proteins (IDPs) or short peptides. However, the molecular mechanisms underlying the formation of biomolecular condensates have not been fully understood. In this study, the authors demonstrate that the LLPS propensity, dynamics, and encapsulation efficiency of designed peptide condensates can be tuned by subtle changes to the peptide composition. This sequence-structure-function correlation could pave the way for the future development of compartments for various applications.
NATURE COMMUNICATIONS
(2023)
Review
Chemistry, Multidisciplinary
Kadi L. Saar, Daoyuan Qian, Lydia L. Good, Alexey S. Morgunov, Rosana Collepardo-Guevara, Robert B. Best, Tuomas P. J. Knowles
Summary: Biomolecular condensation processes are fundamental mechanisms that living cells utilize to organize biomolecules in time and space, leading to the formation of membraneless organelles. Computational methods, including theoretical methods, physics-driven simulations, and data-driven machine learning methods, provide a unique perspective to study biomolecular condensation and offer advantages such as high resolution and scale. This review discusses the recent progress and limitations of these computational approaches and highlights the challenges in understanding the molecular driving forces and biological roles of biomolecular condensation in health and disease.
Article
Multidisciplinary Sciences
Andrew Z. Lin, Kiersten M. Ruff, Furqan Dar, Ameya Jalihal, Matthew R. King, Jared M. Lalmansingh, Ammon E. Posey, Nadia A. Erkamp, Ian Seim, Amy S. Gladfelter, Rohit V. Pappu
Summary: The authors report that protein-RNA condensates with shared proteins and distinct RNAs can form and persist in vitro and in cells as distinct entities if the nonshared RNA molecules are dynamically arrested, but the shared protein components are dynamically exchangeable.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Agustin Mangiarotti, Nannan Chen, Ziliang Zhao, Reinhard Lipowsky, Rumiana Dimova
Summary: Cells compartmentalize their interiors into liquid-like condensates, and these condensates can interact with membranes, leading to morphological transformations. This study demonstrates that the interaction between protein condensates and membranes can result in two wetting transitions, and the observed morphologies are influenced by adhesion, membrane elasticity, and interfacial tension.
NATURE COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Yifan Dai, Mina Farag, Dongheon Lee, Xiangze Zeng, Kyeri Kim, Hye-in Son, Xiao Guo, Jonathan Su, Nikhil Peterson, Javid Mohammed, Max Ney, Daniel Mark Shapiro, Rohit V. Pappu, Ashutosh Chilkoti, Lingchong You
Summary: The formation of biomolecular condensates through associative and segregative phase transitions is crucial for controlling cellular functions. This inspired the design of synthetic systems, but most research has focused on phase behaviors in a test tube. In this study, a rational engineering approach was used to program the formation and physical properties of synthetic condensates, achieving specific cellular functions such as plasmid sequestration and transcription regulation in bacteria, and protein circuit modulation in mammalian cells. This approach lays the foundation for engineering designer condensates for synthetic biology applications.
NATURE CHEMICAL BIOLOGY
(2023)
Article
Multidisciplinary Sciences
Agustin Mangiarotti, Macarena Siri, Nicky W. Tam, Ziliang Zhao, Leonel Malacrida, Rumiana Dimova
Summary: Membrane wetting by biomolecular condensates plays an important role in cell biology, but the molecular mechanisms behind this phenomenon are still not well understood. Using nano-environmental sensors and advanced imaging microscopy, the study investigated the formation of protein condensates and their interaction with lipid membranes. The findings suggest a correlation between wetting affinity and lipid packing.
NATURE COMMUNICATIONS
(2023)
Article
Biology
Vijayaraghavan Rangachari
Summary: Unprecedented discoveries have revealed the presence of biomolecular condensates (BCs) in diverse organisms and their involvement in biological functions. Most BCs involve the coacervation of RNA and proteins through liquid-liquid phase separation (LLPS), providing a means for reversible spatiotemporal control of cellular processes. This Perspective discusses the co-evolution of BCs as complex microcompartments alongside membrane-bound organelles in cells.
COMMUNICATIONS BIOLOGY
(2023)
Article
Cell Biology
Daxiao Sun, Isabel LuValle-Burke, Karina Pombo-Garcia, Alf Honigmann
Summary: This review discusses the role of phase separation of multivalent proteins in the assembly of cellular junctional complexes and summarizes recent evidence.
CURRENT OPINION IN CELL BIOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Selena M. Sagan, Stephanie C. Weber
Summary: Viruses compartmentalize their replication and assembly machinery to evade detection and concentrate necessary proteins and nucleic acids. Recent evidence shows RNA and DNA viruses form replication organelles and assembly sites through phase separation. Two types of viral protein, antiterminators and nucleocapsid proteins, regulate the biogenesis of these compartments. This review focuses on how RNA viruses establish replication organelles and assembly sites through phase separation, and suggests that all viruses rely on phase separation to complete the infectious cycle.
TRENDS IN BIOCHEMICAL SCIENCES
(2023)
Editorial Material
Biophysics
Ashish Joshi, Samrat Mukhopadhyay
Summary: The formation of biomolecular condensates is a new biophysical principle for subcellular compartmentalization, enabling the regulation of complex biomolecular reactions. This Research Highlight summarizes papers published in Biophysical Journal from 2021 to 2022, which provide insights into the formation of biomolecular condensates through protein phase separation with or without nucleic acids.
BIOPHYSICAL JOURNAL
(2023)
Article
Biochemistry & Molecular Biology
Daniel Scholl, Ashok A. Deniz
Summary: The emergence of biomolecular condensation and liquid-liquid phase separation (LLPS) adds complexity to our understanding of cell and molecular biology. Condensates are implicated in both physiology and human disease. Molecular characterization of condensates and their effects on constituent molecules is limited. Recent studies provide insights into the structure, dynamics, and interactions of proteins involved in condensation, which can help modulate the behavior of condensate systems. The unique environment of droplet surfaces and the effects of topological constraints and physical exclusion on condensate properties are also discussed.
JOURNAL OF MOLECULAR BIOLOGY
(2022)
Article
Chemistry, Physical
Jin Zhou, Ying Cai, Yuting Wan, Bohang Wu, Jinbo Liu, Xinxin Zhang, Weiwei Hu, Martien A. Cohen Stuart, Junyou Wang
Summary: This study presents a sequential coacervation process for efficiently isolating and purifying proteins with different isoelectric points (pIs) from a mixed solution. By introducing a suitable polyelectrolyte at the appropriate pH and ionic strength, selective complex coacervation can be achieved, enabling the separation of proteins with high purity.
JOURNAL OF COLLOID AND INTERFACE SCIENCE
(2023)
Article
Multidisciplinary Sciences
Fleurie M. Kelley, Bruna Favetta, Roshan Mammen Regy, Jeetain Mittal, Benjamin S. Schuster
Summary: Cells contain membraneless compartments formed by liquid-liquid phase separation, including biomolecular condensates with complex morphologies. The size and structure of these condensates must be regulated for proper biological function. Amphiphilic, surfactant-like proteins may play a significant role in regulating the structure and function of biomolecular condensates.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Chemistry, Physical
Divya Kota, Huan-Xiang Zhou
Summary: This study found that macromolecular regulators have effects on the material properties of biomolecular condensates, including phase equilibrium, interfacial tension, viscoelasticity, fusion speed, etc. These results illustrate the opportunities for tuning material properties.
JOURNAL OF PHYSICAL CHEMISTRY LETTERS
(2022)
Article
Biochemistry & Molecular Biology
Haneul Yoo, Jared A. M. Bard, Evgeny Pilipenko, D. Allan Drummond
Summary: Recent research has shown that heat-induced protein aggregates are actually evolved adaptive biomolecular condensates, with chaperone activity contributing to their regulation, rather than toxic misfolding as previously thought. The yeast disaggregation system can rapidly disperse heat-induced biomolecular condensates, differing in molecular requirements and mechanistic behavior from heat-induced aggregate dispersal. This work highlights the need to expand the proteotoxic interpretation of the heat shock response to include adaptive, chaperone-mediated regulation.
Review
Polymer Science
Justin M. Horn, Rachel A. Kapelner, Allie C. Obermeyer
Review
Biochemistry & Molecular Biology
Justin M. Horn, Allie C. Obermeyer
Summary: Protein-based therapeutics are a rapidly growing field in disease treatment, and successful intracellular delivery is crucial for expanding their applications. Various methods for modifying proteins and peptides have been developed to improve their cellular translocation efficiency. General strategies such as chemical supercharging or inclusion of cell-penetrating motifs can facilitate intracellular delivery of proteins.
Review
Chemistry, Multidisciplinary
Theanne N. Schiros, Christopher Z. Mosher, Yuncan Zhu, Thomas Bina, Valentina Gomez, Chui Lian Lee, Helen H. Lu, Allie C. Obermeyer
Summary: Current textile production processes, while providing materials with desirable performance properties, are major contributors to global greenhouse gas emissions, microplastic pollution, and toxic wastewater. However, bioengineering of fibers and textiles offers avenues to improve their environmental impacts and technical performance, leading to a more sustainable production.
Article
Multidisciplinary Sciences
Vivian Yeong, Jou-wen Wang, Justin M. Horn, Allie C. Obermeyer
Summary: Phase separation provides intracellular organization and is crucial for cellular processes. This study demonstrates the use of short cationic peptide tags for engineering protein phase separation in bacteria, showing their broad applicability and impact on condensate formation.
NATURE COMMUNICATIONS
(2022)
Article
Chemistry, Multidisciplinary
Supraja S. Chittari, Allie C. Obermeyer, Abigail S. Knight
Summary: Through studying thermoresponsive copolymers, it is found that the nonequilibrium thermal hysteretic behavior is influenced by composition and stimulus path. Analysis of heat-cool cycles reveals that hysteresis in copolymers varies based on side chain length and hydrophobicity. The temperature ramp rate also affects hysteresis, as optimized temperature protocols can trap the material in insoluble states. This study uncovers fundamental principles for harnessing out-of-equilibrium effects in synthetic soft materials.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Multidisciplinary
Nisha Modi, Siwei Chen, Imelda N. A. Adjei, Briana L. L. Franco, Kyle J. M. Bishop, Allie C. C. Obermeyer
Summary: Membraneless organelles use phase separation and enzymatic reactions for cellular regulation. In this study, a pH-responsive catalytic droplet model was investigated, where enzyme activity induces a pH change that triggers condensate dissolution. The effect of enzymatic reaction on phase separation depends on droplet size. Reaction-diffusion models showed that larger droplets support greater local pH changes and enhanced dissolution.
Article
Chemistry, Multidisciplinary
Rachel A. Kapelner, Rachel S. Fisher, Shana Elbaum-Garfinkle, Allie C. Obermeyer
Summary: This study investigates the potential of using polyelectrolyte complex micelles as protein delivery vehicles and highlights the significant influence of protein charge and charge distribution on complex stability and delivery efficiency. Requirements for effectively delivering proteins under physiological conditions were identified using a model system.
Article
Chemistry, Physical
Justin M. Horn, Yuncan Zhu, So Yeon Ahn, Allie C. Obermeyer
Summary: Intrinsically disordered polypeptides with negative charge were produced and used to create protein-based polyelectrolyte complexes. These complexes exhibited rich phase behavior and were sensitive to various factors, demonstrating both robust expression and stimuli-responsive properties of the intrinsically disordered peptides. These results suggest the potential of intrinsically disordered peptides as easily producible, biocompatible substitutes for synthetic polyelectrolytes.
Article
Chemistry, Physical
Nicholas A. Zervoudis, Allie C. Obermeyer
Summary: This study investigated the impact of protein-specific parameters on complex coacervation, focusing on the effects of protein charge patterning on phase behavior. The results showed that charge patterning dictates the protein's binodal phase boundary, indicating that even modest changes in tag polypeptide sequence can alter coacervation thermodynamics and phase behavior.
Article
Chemistry, Multidisciplinary
Vivian Yeong, Emily G. Werth, Lewis M. Brown, Allie C. Obermeyer
ACS CENTRAL SCIENCE
(2020)
Article
Chemistry, Multidisciplinary
Rachel A. Kapelner, Allie C. Obermeyer