In recent years, the physical phenomenon of liquid-liquid phase separation has been widely introduced into biological research. Membrane-free organelles have been found to exist in cells that were driven by liquid-liquid phase separation. Intermolecular multivalent interactions can drive liquid-liquid phase separation to form condensates that are independent of other substances in the environment and thus can play an effective role in regulating multiple biological processes in the cell. The way of cell death has also long been a focus in multiple research. In the face of various stresses, cell death-related mechanisms are crucial for maintaining cellular homeostasis and regulating cell fate. With the in-depth study of cell death pathways, it has been found that the process of cell death was also accompanied by the regulation of liquid-liquid phase separation and played a key role. Therefore, this review summarized the roles of liquid-liquid phase separation in various cell death pathways, and explored the regulation of cell fate by liquid-liquid phase separation, with the expectation that the exploration of the mechanism of liquid-liquid phase separation would provide new insights into the treatment of diseases caused by regulated cell death.
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http://dx.doi.org/10.1016/j.cellsig.2024.111215 | DOI Listing |
Nucleic Acids Res
January 2025
Department of Genome Sciences, University of Virginia, PO Box 800717, Charlottesville, VA 22908, USA.
Many transcription factors (TFs) have been shown to bind to super-enhancers, forming transcriptional condensates to activate transcription in various cellular systems. However, the genomic and epigenomic determinants of phase-separated transcriptional condensate formation remain poorly understood. Questions regarding which TFs tend to associate with transcriptional condensates and what factors influence their association are largely unanswered.
View Article and Find Full Text PDFCell Rep Phys Sci
November 2024
Program in Computational Biology and Bioinformatics, Yale University, New Haven, CT 06520, USA.
Graph neural networks (GNNs) have emerged as powerful tools for representation learning. Their efficacy depends on their having an optimal underlying graph. In many cases, the most relevant information comes from specific subgraphs.
View Article and Find Full Text PDFMater Horiz
January 2025
Bioorganic Chemistry Laboratory, New Chemistry Unit, Jawaharlal Nehru Centre for Advanced Scientific Research (JNCASR), Jakkur P.O., Bengaluru 560064, Karnataka, India.
Enzyme-instructed self-assembly (EISA) is a promising approach to anti-cancer therapeutics due to its precise targeting and unique cell death mechanism. In this study, we introduce a small molecule, DN6, which undergoes nitroreductase (NTR)-responsive liquid-liquid phase separation (LLPS) followed by a liquid-to-solid phase transition (LST) through a gel-like intermediate state, resulting in the formation of nanoaggregates with spatiotemporal control. The reduced form of DN6 (DN6R), owing to its aggregation-induced emission (AIE) and mitochondria-targeting capabilities, has been employed for organelle-specific imaging of tumor hypoxia.
View Article and Find Full Text PDFBiomacromolecules
January 2025
Department of Applied Chemistry, Kyung Hee University, Yongin, Gyeonggi 17104, South Korea.
This study proposes fluorenylmethoxycarbonyl (Fmoc)-protected single amino acids (Fmoc-AAs) as a minimalistic model system to investigate liquid-liquid phase separation (LLPS) and the elusive liquid-to-solid transition of condensates. We demonstrated that Fmoc-AAs exhibit LLPS depending on the pH and ionic strength, primarily driven by hydrophobic interactions. Systematic examination of the conditions under which each Fmoc-AA undergoes LLPS revealed distinct residue-dependent trends in the critical concentrations and phase behavior.
View Article and Find Full Text PDFJ Am Chem Soc
January 2025
Center for Sustainable Materials (SusMat), School of Materials Science and Engineering, Nanyang Technological University, Singapore 639798, Singapore.
Complex coacervation is a form of liquid-liquid phase separation, whereby two types of macromolecules, usually bearing opposite net charges, self-assemble into dense microdroplets driven by weak molecular interactions. Peptide-based coacervates have recently emerged as promising carriers to deliver large macromolecules (nucleic acids, proteins and complex thereof) inside cells. Thus, it is essential to understand their assembly/disassembly mechanisms at the molecular level in order to tune the thermodynamics of coacervates formation and the kinetics of cargo release upon entering the cell.
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