Article
Chemistry, Physical
Anna Bratek-Skicki, Margot Van Nerom, Dominique Maes, Peter Tompa
Summary: Biomolecular condensates are membraneless organelles formed through liquid-liquid phase separation that can concentrate a variety of molecules in cells. They are highly dynamic and play crucial roles in cellular organization and physiology, with links to diseases like neurodegenerative disorders and cancer. This review discusses the mechanisms, dynamics, and evolution of these biological colloids, particularly focusing on their surface properties and interactions with other cellular components. Experimental approaches for characterizing the formation, interactions, and functions of these cellular colloidal organelles are also summarized.
ADVANCES IN COLLOID AND INTERFACE SCIENCE
(2022)
Review
Biochemistry & Molecular Biology
Katarzyna Soltys, Andrzej Ozyhar
Summary: Eukaryotic cells are composed of different bio-macromolecules that are divided into compartments called organelles providing optimal microenvironments for many cellular processes. The specific type of organelles is membraneless organelles, formed via liquid-liquid phase separation driven by weak multivalent interactions between specific bio-macromolecules. Intrinsically disordered regions play a key role in this phenomenon.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Materials Science, Multidisciplinary
Jianhui Liu, Fariza Zhorabek, Ying Chau
Summary: Membraneless organelles (MLOs) are phase-separated liquid compartments in cells that provide precise control over biomolecules and metabolism. Their formation relies on weak non-covalent interactions of intrinsically disordered proteins (IDPs). Understanding the design and behavior of IDPs in liquid-liquid phase separation is crucial for understanding the contributions of MLOs to cellular physiology and disease. This knowledge can also inspire the design of biomaterials and systems in various fields.
Review
Biochemical Research Methods
Chao Hou, Haotai Xie, Yang Fu, Yao Ma, Tingting Li
Summary: Cells are compartmentalized by membrane-bounded and membraneless organelles for temporal and spatial regulation. MLOs, like nucleoli and stress granules, form liquid droplets via liquid-liquid phase separation, accelerating biochemical reactions and protecting cells. Dysfunction of MLOs is linked to various pathological processes, and MloDisDB aims to gather and centralize information on relations between MLOs and diseases.
BRIEFINGS IN BIOINFORMATICS
(2021)
Review
Chemistry, Physical
N. Amy Yewdall, Alain A. M. Andre, Tiemei Lu, Evan Spruijt
Summary: Coacervates are condensed liquid-like droplets formed by oppositely charged polymeric molecules, with remarkable material properties that have been extensively studied. They play an important role in the formation of membraneless organelles in living cells. Well-characterized coacervates can serve as useful models to better understand specific aspects of membraneless organelles.
CURRENT OPINION IN COLLOID & INTERFACE SCIENCE
(2021)
Article
Chemistry, Multidisciplinary
Yanwen Zhang, Shixin Wang, Yuling Yan, Xiaoxiao He, Zefeng Wang, Shaohong Zhou, Xiaohai Yang, Kemin Wang, Jianbo Liu
Summary: Implanting artificial organelles in living cells can correct cellular dysfunctionalities for cell repair and biomedical applications. In this study, phase-separated bienzyme-loaded coacervate microdroplets were used as a model of artificial membraneless organelles to produce nitric oxide (NO) for correcting cellular NO deficiency in dysfunctional cells. The coacervate microdroplets were prepared using liquid-liquid phase separation and implanted into NO-deficient dysfunctional cells, resulting in enhanced NO production and inhibition of clot formation. This research demonstrates the potential of artificial organelles in cell engineering and medical therapy.
SCIENCE CHINA-CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Jianhui Liu, Fariza Zhorabek, Tianfu Zhang, Jacky W. Y. Lam, Ben Zhong Tang, Ying Chau
Summary: This study demonstrates the enrichment, recruitment, and release of multifaceted cargoes using a minimalist artificial membraneless organelle (AMLO) driven by liquid-liquid phase separation. The AMLO shows up to 10(5)-fold enrichment of cargoes, and recruitment and release can be triggered by variations in temperature, pH, and ionic strength. Additionally, the study achieves effective and reversible control of aggregation-induced emission, making the AMLO a versatile platform for potential drug delivery and biosensor applications.
Article
Biochemistry & Molecular Biology
Fernando Orti, Alvaro M. Navarro, Andres Rabinovich, Shoshana J. Wodak, Cristina Marino-Buslje
Summary: Attention has been focused on membraneless organelles (MLO) formed by proteins in recent years due to their dynamic exchange with the cellular milieu. Dysregulation of liquid-liquid phase separation processes (LLPS) may lead to various diseases. Four recently published databases provide valuable information on MLO proteins, enabling better understanding of phase separation and the discovery of potential new proteins involved in this important cellular process.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2021)
Article
Biochemistry & Molecular Biology
Mikael Garabedian, Wentao Wang, Jorge B. Dabdoub, Michelle Tong, Reese M. Caldwell, William Benman, Benjamin S. Schuster, Alexander Deiters, Matthew C. Good
Summary: The subcellular compartmentalization of macromolecules is essential for controlling biochemical reactions by increasing flux and preventing inhibitory interactions. We have developed a synthetic membraneless organelle platform that can control endogenous cellular activities by sequestering and insulating native proteins. By relocalizing targeted enzymes to synthetic condensates, we are able to efficiently regulate cellular behaviors such as proliferation, division, and cytoskeletal organization, and demonstrate strategies for releasing cargo from condensates to switch cells between functional states. These synthetic organelles offer a powerful and versatile approach to controlling cell decision-making in various model systems, with broad applications in cellular engineering.
NATURE CHEMICAL BIOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Qingchuan Li, Qingchun Song, Wei Guo, Yang Cao, Xinyu Cui, Dairong Chen, Ho Cheung Shum
Summary: In this study, a synthetic droplet called segregative-associative (SA) droplets is developed to mimic membraneless organelles (MLOs) in cells. These SA droplets exhibit complex phase behaviors similar to MLOs and can cluster lipid vesicles like synapsin condensates.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
Qi-Hong Zhao, Fang-Hao Cao, Zhen-Hong Luo, Wilhelm T. S. Huck, Nan-Nan Deng
Summary: This study successfully achieved photoswitchable molecular transport between programmable membraneless DNA coacervates in synthetic microcompartments using droplet microfluidics, mimicking controlled bi-directional communication inside cells and providing a promising new route for assembling multicompartment artificial cells with functional networks.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Physical
Chen Chen, Ruiqin Yi, Motoko Igisu, Chie Sakaguchi, Rehana Afrin, Christian Potiszil, Tak Kunihiro, Katsura Kobayashi, Eizo Nakamura, Yuichiro Ueno, Andre Antunes, Anna Wang, Kuhan Chandru, Jihua Hao, Tony Z. Jia
Summary: Alpha-hydroxy acids can react to form polyester gels that can arrange into membraneless microdroplets. These microdroplets, proposed as protocells, can segregate and compartmentalize primitive molecules/reactions. Different primitive aqueous environments with various salts could have allowed the formation of polyester microdroplets. This study investigates the interactions between polyester and salt ions, using spectroscopic and biophysical methods to analyze salt uptake and its effects on microdroplet properties.
Article
Chemistry, Multidisciplinary
Fariza Zhorabek, Manisha Sandupama Abesekara, Jianhui Liu, Xin Dai, Jinqing Huang, Ying Chau
Summary: A biomimetic platform for building synthetic multiphasic condensates using engineered multivalent polymer-oligopeptide hybrids is presented. This platform enables the replication of the hierarchical multicompartment organization found in intracellular membraneless organelles, allowing for the enrichment and segregation of functional biomolecules.
Article
Cell Biology
Viviana Scoca, Renaud Morin, Maxence Collard, Jean-Yves Tinevez, Francesca Di Nunzio
Summary: HIV virus hijacks host cells by utilizing a biological phenomenon called liquid-liquid phase separation to form HIV-induced membraneless organelles (HIV-1 MLOs), which serve as hubs for viral replication and transcription. These structures play a crucial role in promoting the integration and replication of the virus within the host.
JOURNAL OF MOLECULAR CELL BIOLOGY
(2023)
Article
Virology
Hana Mahmutefendic Lucin, Silvija Lukanovic Juric, Marina Marcelic, Igor Stimac, Ivona Viduka, Gordana Blagojevic Zagorac, Berislav Lisnic, Zsolt Ruzsics, Pero Lucin
Summary: This study visualized the behavior of viral proteins and DNA during murine cytomegalovirus (MCMV) infection, revealing the details of nuclear events. It was found that viral proteins and DNA form membraneless assemblies in the nucleus, which mature into the nuclear replication compartment and cytoplasmic assembly compartment. These findings are important for further understanding the replication cycle of beta-herpesviruses.
Article
Chemistry, Analytical
Ikumi Onohara, Masato Suzuki, Yushi Isozaki, Kanta Tsumoto, Masahiro Tomita, Tomoyuki Yasukawa
Summary: This paper investigates the electrofusion of splenocytes and myeloma cells using an asymmetric electric field in a rectangular microwell array. Different cells with varying diameters are captured using different electric field strengths before being fused together.
ANALYTICAL SCIENCES
(2022)
Article
Chemistry, Multidisciplinary
Azusa Oshima, Kohei Nakanishi, Nahoko Kasai, Hiroshi Nakashima, Kanta Tsumoto, Koji Sumitomo
Summary: This study investigates membrane protein reconstitution and fusion dynamics using artificial planar bilayer lipid membranes (BLMs) and baculovirus-budded virus (BV) systems. The results demonstrate that BV fusion with BLMs is enhanced at lower pH and can effectively reconstitute membrane proteins. The study reveals the promising potential of BV fusion for the development of biodevices to examine membrane protein activity.
Article
Materials Science, Biomaterials
Takashi Nishio, Tomoya Masaoka, Yuko Yoshikawa, Koichiro Sadakane, Takahiro Kenmotsu, Helmut Schiessel, Kenichi Yoshikawa
Summary: The effect of monovalent cations on a cell-free transcription-translation (TX-TL) system was studied using a luciferase assay. Rb+ was found to be the most efficient in promoting TX-TL, while Li+, Na+, and (CH3)(4)N+ exhibited inhibitory effects. Similar promotion/inhibition effects were observed in cell-free translation alone using an mRNA template.
Article
Biochemistry & Molecular Biology
Jekaterina Erenpreisa, Alessandro Giuliani, Kenichi Yoshikawa, Martin Falk, Georg Hildenbrand, Kristine Salmina, Talivaldis Freivalds, Ninel Vainshelbaum, Jonas Weidner, Aaron Sievers, Gotz Pilarczyk, Michael Hausmann
Summary: Complex functioning of the genome in the cell nucleus is controlled at different levels, including the DNA base sequence, epigenetic pathways, and genome architecture. This article reviews recent research on integrating these levels of genome expression regulation and discusses the conclusions from an international symposium held in Riga, Latvia, which addressed novel aspects of the topic.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Polymer Science
Kohei Fujino, Takashi Nishio, Keita Fujioka, Yuko Yoshikawa, Takahiro Kenmotsu, Kenichi Yoshikawa
Summary: This report investigates the effects of alcohols on gene expression and the mechanical properties of DNA molecules. It shows that ethanol and 2-propanol significantly increase gene expression levels, while 1-propanol has an inhibitory effect. The observation of single DNA molecules reveals that 1-propanol greatly enhances the mechanical properties of DNA, while ethanol and 2-propanol have weaker effects. These findings demonstrate a correlation between the activation/inhibition effects of alcohol isomers on gene expression and the viscoelastic properties of DNA molecules.
Article
Biochemistry & Molecular Biology
Takashi Nishio, Yohji Shimada, Yuko Yoshikawa, Takahiro Kenmotsu, Helmut Schiessel, Kenichi Yoshikawa
Summary: In this study, we used an in vitro cell-free system with spermine to investigate the effect of daunomycin (DM) on gene expression. We found that DM exhibits a bimodal effect on gene expression, promoting at lower concentrations and inhibiting at higher concentrations. Through atomic force microscopy observation, we observed that DM destroys flower-like conformations of DNA induced by spermine, resulting in double-strand breaks. These newly revealed effects of DM on gene expression and DNA structure will contribute to the development and refinement of anticancer therapy chemicals.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Physics, Multidisciplinary
Maho Kuroda, Satoshi Takatori, Takahiro Kenmotsu, Kenichi Yoshikawa, Chwen-Yang Shew
Summary: Macroscopic systems mimicking microscopic systems were used to study the organization of macro-molecules in a confined space. Experimental and numerical models showed that the behavior of a large particle interacting with small particles under different boundary conditions is influenced by crowding. Membrane stiffness was found to affect the organization of biopolymers and may play a role in cellular dynamics.
JOURNAL OF THE PHYSICAL SOCIETY OF JAPAN
(2023)
Article
Chemistry, Multidisciplinary
Mayu Shono, Gen Honda, Miho Yanagisawa, Kenichi Yoshikawa, Akihisa Shioi
Summary: In this study, a one-step method using glass capillaries and a polymer blend of PEG and gelatin is discussed for producing uniform cell-sized microgels. The method involves phase separation and gelation of the polymer blend upon decreasing temperature, leading to the formation of linearly aligned, uniformly sized gelatin microgels. The addition of DNA prevents coalescence of the microdroplets. This novel method has potential applications in biopolymers and cellular models.
Article
Chemistry, Multidisciplinary
Hiroki Sakuta, Naoki Nakatani, Takayuki Torisawa, Yutaka Sumino, Kanta Tsumoto, Kazuhiro Oiwa, Kenichi Yoshikawa
Summary: Water phase separation in cells can lead to mechanical motion by entrapping protein motors and generating vortex flow inside cell-sized droplets. This study reveals that the water phase separation interface can drive translational motion of droplets by spontaneously entrapping kinesins and microtubules and generating vortex flow. The findings highlight the importance of water phase separation in both chemical and mechanical processes.
COMMUNICATIONS CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Misako Nishigami, Yuki Uno, Kanta Tsumoto
Summary: In this study, the activation of GP64 and membrane fusion on giant liposomes were triggered using NPE-caged-proton. It was found that BVs prefer phosphatidylserine as they accumulated around GUVs with DOPS before the fusion reaction. This research provides valuable insights into the behavior of viruses under different chemical and biochemical environments.
Article
Chemistry, Physical
Yuki Kanakubo, Chiho Watanabe, Johtaro Yamamoto, Naoya Yanagisawa, Hiroki Sakuta, Arash Nikoubashman, Miho Yanagisawa
Summary: Living cells are characterized by the confinement of macromolecules at high concentrations. This study shows that this confinement-induced heterogeneity also occurs in single-component polymer solutions. The structural heterogeneity leads to slower transport of small molecules in cell-sized droplets compared to bulk solutions. Molecular simulations support the confinement-induced distribution by polymer length and the effect of conformational entropy.
Editorial Material
Biology
Pasquale Stano, Kanta Tsumoto
Article
Chemistry, Multidisciplinary
Mayu Shono, Fumika Fujita, Kenichi Yoshikawa, Akihisa Shioi
Summary: Stable cell-sized droplets entrapping DNA molecules are generated through micro segregation. Measurements of electrification and Zeta potentials confirmed the presence of negatively charged droplets trapping the DNA.
