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Stress stimulation-mediated liquid-liquid phase separation is a key activity in living organisms, but its biophysical characteristics are poorly understood. Here, we report a UV-light stress stimulation behaviour in a binary community of synthetic protocells of condensates and proteinosomes, showing that condensates could behave like Condensate Pumps to enable a stepwise controlled transmembrane mass transfer regardless of the permeability barrier of proteinosomes. The stimulation mechanism of interfacial tension-induced proteinosome deformation and transient high osmotic pressure arisen by the dissociation of condensate is proposed. Accordingly, under UV-light stress stimulation, unexpected characteristics could be triggered by transmembrane pumping oversized biomacromolecules into proteinosomes including liquid-liquid reentrant phase separation, DNA unwinding, and protein synthesis. Therefore, our results not only reveal unique physical principles and potential characteristics of macromolecular assemblies at droplet-membrane interface but also highlight a pathway for transmembrane transport of biomacromolecules which is anticipated to serve as a powerful technique to inducing higher-order behaviour in synthetic protocells community.
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http://dx.doi.org/10.1038/s41467-025-60541-7 | DOI Listing |
Biophys Chem
September 2025
Department of Biophysics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran.
A comprehensive understanding of the molecular mechanism underlying the Liquid-Liquid Phase Separation (LLPS) pathway of LCD-TDP43 remains a challenge in the context of its neuropathogenesis. The primary driving force behind the TDP-43 LLPS is the interplay of hydrophobic interactions reinforced by aromatic residues. This study presents a novel, convenient, sensitive, and probe-free approach using excitation-emission matrix (EEM) fluorescence to monitor the microenvironment of aromatic residues and π-π stacking interactions during different stages of the LLPS pathway.
View Article and Find Full Text PDFAdv Biol Regul
September 2025
Laboratory of Cancer Cell Architecture, Institute of Biochemistry and Experimental Oncology, First Faculty of Medicine, Charles University, Prague, Czech Republic. Electronic address:
Biomolecular condensates (BMCs) are membrane-less organelles formed through liquid-liquid phase separation, primarily driven by multivalent interactions between scaffold and client molecules. These dynamic compartments enable cells to spatially and temporally organize biochemical reactions by locally concentrating specific biomolecules, thereby enhancing the frequency of productive molecular interactions and increasing reaction rates. BMCs are integral to normal cellular physiology, with well-characterized examples including the nucleolus and Cajal bodies.
View Article and Find Full Text PDFPlant J
September 2025
Temasek Life Sciences Laboratory, 1 Research Link, National University of Singapore, Singapore, 117604, Singapore.
Salicylic acid (SA), a long-characterized defense hormone, is increasingly recognized for its roles in plant growth and development. However, its involvement in mediating plant growth responses to environmental cues remains less understood. Here, we show that SA negatively affects thermomorphogenic growth in Arabidopsis thaliana.
View Article and Find Full Text PDFBiochemistry
September 2025
Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, Maryland 21205, United States.
SAMHD1 (SAM domain and HD domain-containing protein 1) is a deoxynucleoside triphosphate triphosphohydrolase (dNTPase) with functions in viral restriction, R-loop resolution, DNA repair, telomere maintenance, ssRNA homeostasis, and regulation of self-nucleic acids. As a dNTPase, SAMHD1 functions as an allosterically activated tetramer, where binding of GTP to the A1 activator site of each monomer initiates dNTP-dependent tetramerization. cEM structures reveal that the nucleic-acid-related functions of SAMHD1 involve binding of guanine residues to the A1 site, leading to oligomeric forms that appear as beads-on-a-string on single-stranded RNA and DNA.
View Article and Find Full Text PDFNat Cell Biol
September 2025
State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China.
The ataxia telangiectasia mutated (ATM) kinase orchestrates the early stages of DNA double-strand break repair by promoting hyperphosphorylation of CtIP, a key step in the initiation of DNA end resection. However, the regulatory mechanisms controlling resection extent remain incompletely understood. Here we identify ERCC6L2 as a key regulator of DNA end resection in response to ATM inhibition.
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