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Camilo A. S. Afanador*, Stéphane Urcun*, Ivo F. Sbalzarini, Stéphane P. A. Bordas, Olga Barrera, Mohammad Mahdi Rajabi, Romain Seil, Anas Obeidat
Mechanics of knee meniscus results from precise balance between material microstructure and synovial fluid viscosity.
PLoS ONE, 20(9) Art. No. e0304440 (2025)
Open Access   PubMed Source   

The meniscus plays a crucial role in the biomechanics of the knee, serving as load transmitter and reducing friction between joints. Understanding the biomechanics of the meniscus is essential to effective treatment of knee injuries and degenerative conditions. This study aims to elucidate the relationship between the porous microstructure of the human knee meniscus and its biomechanical function, specifically focusing on fluid dynamics at the pore scale. Here, we use two central-meniscus samples extracted from a human knee and reconstruct high-resolution geometry models from [Formula: see text]-CT scans. By eroding the channels of the original meniscus geometry, we simulate perturbed microstructures with varying porosities ( 53% to 80%), whilst preserving the connectivity of the porous structure. We numerically solve for the fluid dynamics in the meniscus using a mesh-free particle method, considering various inlet pressure conditions, characterising the fluid flow within the microstructures. The results of the original microstructure associated with a physiological dynamic viscosity of synovial fluid are in accordance with biophysical experiments on menisci. Furthermore, the eroded microstructure with a 33% increase in porosity exhibited a remarkable 120% increase in flow velocity. This emphasises the sensitivity of meniscus physiology to the porous microstructure, showing that detailed computational models can explore physiological and pathological conditions, advancing further knee biomechanics research.
@article{Afanador9041,
author={Camilo A. S. Afanador, Stéphane Urcun, Ivo F. Sbalzarini, Stéphane P. A. Bordas, Olga Barrera, Mohammad Mahdi Rajabi, Romain Seil, Anas Obeidat},
title={Mechanics of knee meniscus results from precise balance between material microstructure and synovial fluid viscosity.},
journal ={PloS one},
volume={20},
issue ={9},
pages={null--null},
year=2025
}

Julia Vorhauser, Theodoros I Roumeliotis, David Coupe, Jacky K Leung, Lu Yu, Kristin Böhlig, Thomas Zerjatke, Ingmar Glauche, André Nadler, Jyoti S Choudhary, Jorg Mansfeld
A redox switch in p21-CDK feedback during G2 phase controls the proliferation-cell cycle exit decision.
Mol Cell, 85(17) 3241-3255 (2025)
Open Access PubMed Source   

Reactive oxygen species (ROS) influence cell proliferation and fate decisions by oxidizing cysteine residues (S-sulfenylation) of proteins, but specific targets and underlying regulatory mechanisms remain poorly defined. Here, we employ redox proteomics to identify cell-cycle-coordinated S-sulfenylation events and investigate their functional role in proliferation control. Although ROS levels rise during cell cycle progression, the overall oxidation of the proteome remains constant, with dynamic S-sulfenylation restricted to a subset of cysteines. Among these, we identify a critical redox-sensitive cysteine residue (C41) in the cyclin-dependent kinase (CDK) inhibitor p21. C41 oxidation regulates the interaction of p21 with CDK2 and CDK4, controlling a double-negative feedback loop that determines p21 stability. When C41 remains reduced, p21's half-life increases in the G2 phase, resulting in more p21 inheritance to daughter cells, suppressing proliferation and promoting senescence after irradiation. Notably, we identify dynamic S-sulfenylation on further cell cycle regulators, implying coordination of cell cycle and redox control.
@article{Vorhauser9054,
author={Julia Vorhauser, Theodoros I Roumeliotis, David Coupe, Jacky K Leung, Lu Yu, Kristin Böhlig, Thomas Zerjatke, Ingmar Glauche, André Nadler, Jyoti S Choudhary, Jorg Mansfeld},
title={A redox switch in p21-CDK feedback during G2 phase controls the proliferation-cell cycle exit decision.},
journal ={Molecular cell},
volume={85},
issue ={17},
pages={3241--3255},
year=2025
}

Patrick M McCall#, Kyoohyun Kim, Anna Shevchenko, Martine Ruer-Gruß, Jan Peychl, Jochen Guck, Andrej Shevchenko, Anthony Hyman, Jan Brugués#
A label-free method for measuring the composition of multicomponent biomolecular condensates.
Nat Chem, Art. No. doi: 10.1038/s41557-025-01928-3 (2025)
Open Access PubMed Source   

Many subcellular compartments are biomolecular condensates made of multiple components, often including several distinct proteins and nucleic acids. However, current tools to measure condensate composition are limited and cannot capture this complexity quantitatively because they either require fluorescent labels, which can perturb composition, or can distinguish only one or two components. Here we describe a label-free method based on quantitative phase imaging and analysis of tie-lines and refractive index to measure the composition of reconstituted condensates with multiple components. We first validate the method empirically in binary mixtures, revealing sequence-encoded density variation and complex ageing dynamics for condensates composed of full-length proteins. We then use analysis of tie-lines and refractive index to simultaneously resolve the concentrations of five macromolecular solutes in multicomponent condensates containing RNA and constructs of multiple RNA-binding proteins. Our measurements reveal an unexpected decoupling of density and composition, highlighting the need to determine molecular stoichiometry in multicomponent condensates. We foresee this approach enabling the study of compositional regulation of condensate properties and function.
@article{McCall9055,
author={Patrick M McCall, Kyoohyun Kim, Anna Shevchenko, Martine Ruer-Gruß, Jan Peychl, Jochen Guck, Andrej Shevchenko, Anthony Hyman, Jan Brugués},
title={A label-free method for measuring the composition of multicomponent biomolecular condensates.},
journal ={Nature chemistry},
volume={},
pages={1--1},
year=2025
}

Bruno C Vellutini#, Marina B Cuenca, Abhijeet Krishna, Alicja Szałapak, Carl D. Modes, Pavel Tomancak#
Patterned invagination prevents mechanical instability during gastrulation.
Nature, Art. No. doi: 10.1038/s41586-025-09480-3 (2025)
Open Access PubMed Source   

Mechanical forces are crucial for driving and shaping tissue morphogenesis during embryonic development1-3. However, their relevance for the evolution of development remains poorly understood4. Here we show that an evolutionary novelty of fly embryos-the patterned embryonic invagination known as the cephalic furrow5-7-has a mechanical role during Drosophila gastrulation. By integrating in vivo experiments and in silico simulations, we demonstrate that the head-trunk boundary of the embryo is under increased compressive stress due to the concurrent formation of mitotic domains and germ band extension and that the cephalic furrow counteracts these stresses, preventing mechanical instabilities during gastrulation. Then, by comparing the genetic patterning of species with and without the cephalic furrow, we find evidence that changes in the expression of the transcription factor buttonhead are associated with the evolution of the cephalic furrow. These results suggest that the cephalic furrow may have evolved through the genetic stabilization of morphogenesis in response to the mechanical challenges of dipteran gastrulation. Together, our findings uncover empirical evidence for how mechanical forces can influence the evolution of morphogenetic innovations in early development.
@article{Vellutini9040,
author={Bruno C Vellutini, Marina B Cuenca, Abhijeet Krishna, Alicja Szałapak, Carl D. Modes, Pavel Tomancak},
title={Patterned invagination prevents mechanical instability during gastrulation.},
journal ={Nature},
volume={},
pages={1--1},
year=2025
}

Naresh Yandrapalli
Bottom-up development of lipid-based synthetic cells for practical applications.
Trends Biotechnol, 43(9) 2150-2169 (2025)
Open Access PubMed Source   

Synthetic cells (SCs) can be engineered from the bottom up to recapitulate the functional properties of natural cells while performing specialized tasks such as drug delivery, biosensors, bioproduction, vaccine development, and even environmental remediation. Recent advances in synthetic biology, biomaterials, and microfluidics have enabled the development of increasingly sophisticated SCs. Transitioning from proof-of-concept demonstrations to practical applications requires a deep understanding of the design principles, materials, and fabrication techniques involved. This review provides a comprehensive overview of the current state of bottom-up SC technology and highlights the most promising approaches and applications. Challenges in the implementation of SCs and their prospects for future applications are also discussed.
@article{Yandrapalli9056,
author={Naresh Yandrapalli},
title={Bottom-up development of lipid-based synthetic cells for practical applications.},
journal ={Trends in biotechnology},
volume={43},
issue ={9},
pages={2150--2169},
year=2025
}

Jessica Thiel, Duran Sürün, Desiree C Brändle, Madeleine Teichert, Stephan R Künzel, Ulrike Friedrich, Andreas Dahl, Kristin Schubert, Ignacy Rzagalinski, Andrej Shevchenko, Sofia Traikov, Peter Mirtschink, Lisa Wagenführ, Frank Buchholz, Kristina Hölig, Torsten Tonn, Romy Kronstein-Wiedemann
Knock Out of miRNA-30a-5p and Reconstitution of the Actin Network Dynamics Partly Restores the Impaired Terminal Erythroid Differentiation during Blood Pharming.
Stem Cell Rev Rep, Art. No. doi: 10.1007/s12015-025-10957-x (2025)
Open Access PubMed Source   

In vitro red blood cell (RBC) production offers a promising complement to conventional blood donation, particularly for patients with rare blood types. Previously, we developed imBMEP-A, the first erythroid cell line derived from reticulocyte progenitors, which maintains robust hemoglobin expression and erythroid differentiation in the presence of erythropoietin (EPO) despite its immortalized state. However, clinical translation remains hindered by the inability to scale up production due to impaired in vitro enucleation of RBC progenitor cell lines. Enhancing enucleation efficiency in imBMEP-A cells involved CRISPR/Cas9-mediated knockout (K.O.) of miR-30a-5p, a key enucleation inhibitor, moderately increasing rates to 3.3 ± 0.4%- 8.9 ± 1.7%. Further investigation of enucleation inefficiencies led to transcriptome and proteome comparisons between imBMEP-miR30a-K.O. cells and hematopoietic stem cells (HSCs). These analyses revealed altered gene expression and protein abundances linked to metabolic transitions, apoptosis promotion, and cytoskeletal regulation. Notably, forced expression of the proto-oncogene c-Myc, required for cell immortalization, emerged as a key driver of these physiological changes. Counteracting these effects required optimization of imBMEP-A cells by activating BCL-XL transcription and knocking out SCIN, which encodes the actin-severing protein scinderin. While BCL-XL is upregulated in normal erythropoiesis, it is downregulated in imBMEP-A. Conversely, SCIN, typically absent in erythroid cells, is highly expressed in imBMEP-A, disrupting actin organization. These interventions improved viability, restored actin network formation, and increased terminal erythropoiesis, yielding 22.1 ± 1.7% more orthochromatic erythroblasts. These findings establish a foundation for optimizing imBMEP-A cells for therapeutic use and advancing the understanding the pathophysiology of erythroleukemia.
@article{Thiel9053,
author={Jessica Thiel, Duran Sürün, Desiree C Brändle, Madeleine Teichert, Stephan R Künzel, Ulrike Friedrich, Andreas Dahl, Kristin Schubert, Ignacy Rzagalinski, Andrej Shevchenko, Sofia Traikov, Peter Mirtschink, Lisa Wagenführ, Frank Buchholz, Kristina Hölig, Torsten Tonn, Romy Kronstein-Wiedemann},
title={Knock Out of miRNA-30a-5p and Reconstitution of the Actin Network Dynamics Partly Restores the Impaired Terminal Erythroid Differentiation during Blood Pharming.},
journal ={Stem cell reviews and reports},
volume={},
pages={1--1},
year=2025
}

Jannik Rothkegel, Sylvia Kaufmann, Michaela Wilsch-Bräuninger, Catarina Lopes, Rita Mateus
Purine Molecular Interactions Determine Anisotropic Shape of Zebrafish Biogenic Crystals.
Small Methods, Art. No. doi: 10.1002/smtd.202401956 (2025)
Open Access PubMed Source   

Across phyla, many organisms self-organize crystals, for functions like vision, pigmentation, and metabolite storage. In zebrafish, a vertebrate known for its crystal-based color patterns, iridophores concentrate purines in membrane-bound organelles, the iridosomes. Inside these vesicles, crystals assemble into large, flat, and thin hexagons following unknown mechanisms that defy typical thermodynamic interactions. Here, we investigate the development of zebrafish iridosomal crystals by using live imaging, cryoFIB-SEM, and novel morphometric analysis pipelines. In doing so, we find that crystal growth predominantly occurs along the b-crystallographic axis, producing their characteristic anisotropic shape. By performing comparative genetic analyses in vivo and reproducing such conditions in silico, we uncover that the zebrafish crystals' in-plane hydrogen bond molecular structure is the main determinant for the observed crystal anisotropy. Macroscopically, the b-axis anisotropy is controlled by the ratio of guanine-to-hypoxanthine in the iridosome, without affecting the other axes. At the atomic level, the extent of the (100) facet anisotropy depends entirely on the type, number, and strength of molecular H-bonds within the crystal lattice. Mechanistically, our work shows that purine diversity and availability inside the zebrafish iridosome is key to form an anisotropic crystal lattice, leading to the observed functional crystal shapes.
@article{Rothkegel9038,
author={Jannik Rothkegel, Sylvia Kaufmann, Michaela Wilsch-Bräuninger, Catarina Lopes, Rita Mateus},
title={Purine Molecular Interactions Determine Anisotropic Shape of Zebrafish Biogenic Crystals.},
journal ={Small methods},
volume={},
pages={1--1},
year=2025
}

Juan M Iglesias-Artola, Kristin Böhlig, Kai Schuhmann, Katelyn C Cook, H Mathilda Lennartz, Milena Schuhmacher, Pavel Barahtjan, Cristina Jiménez López, Radek Šachl, Vannuruswamy Garikapati, Karina Pombo-Garcia, Annett Lohmann, Petra Riegerová, Martin Hof, Björn Drobot, Andrej Shevchenko, Alf Honigmann#, André Nadler#
Quantitative imaging of lipid transport in mammalian cells.
Nature, ( ) Art. No. doi: 10.1038/s41586-025-09432-x (2025)
Open Access PubMed Source   

Eukaryotic cells produce over 1,000 different lipid species that tune organelle membrane properties, control signalling and store energy1,2. How lipid species are selectively sorted between organelles to maintain specific membrane identities is largely unclear, owing to the difficulty of imaging lipid transport in cells3. Here we measured the retrograde transport and metabolism of individual lipid species in mammalian cells using time-resolved fluorescence imaging of bifunctional lipid probes in combination with ultra-high-resolution mass spectrometry and mathematical modelling. Quantification of lipid flux between organelles revealed that directional, non-vesicular lipid transport is responsible for fast, species-selective lipid sorting, in contrast to the slow, unspecific vesicular membrane trafficking. Using genetic perturbations, we found that coupling between energy-dependent lipid flipping and non-vesicular transport is a mechanism for directional lipid transport. Comparison of metabolic conversion and transport rates showed that non-vesicular transport dominates the organelle distribution of lipids, while species-specific phospholipid metabolism controls neutral lipid accumulation. Our results provide the first quantitative map of retrograde lipid flux in cells4. We anticipate that our pipeline for mapping of lipid flux through physical and chemical space in cells will boost our understanding of lipids in cell biology and disease.
@article{Iglesias-Artola9051,
author={Juan M Iglesias-Artola, Kristin Böhlig, Kai Schuhmann, Katelyn C Cook, H Mathilda Lennartz, Milena Schuhmacher, Pavel Barahtjan, Cristina Jiménez López, Radek Šachl, Vannuruswamy Garikapati, Karina Pombo-Garcia, Annett Lohmann, Petra Riegerová, Martin Hof, Björn Drobot, Andrej Shevchenko, Alf Honigmann, André Nadler},
title={Quantitative imaging of lipid transport in mammalian cells.},
journal ={Nature},
volume={},
issue ={ },
pages={1--1},
year=2025
}

Hannes Ausserwöger*, Ella de Csilléry*, Daoyuan Qian*, Georg Krainer*, Timothy J Welsh, Tomas Sneideris, Titus Franzmann, Seema Qamar, Nadia A Erkamp, Jonathan Nixon-Abell, Mrityunjoy Kar, Peter St George-Hyslop, Anthony Hyman, Simon Alberti, Rohit V Pappu, Tuomas P J Knowles
Quantifying collective interactions in biomolecular phase separation.
Nat Commun, 16(1) Art. No. 7724 (2025)
Open Access PubMed Source   

Biomolecular phase separation is an emerging theme for protein assembly and cellular organisation. The collective forces driving such condensation, however, remain challenging to characterise. Here we show that tracking the dilute phase concentration of only one component suffices to quantify composition and energetics of multicomponent condensates. Applying this assay to several disease- and stress-related proteins, we find that monovalent ions can either deplete from or enrich within the dense phase in a context-dependent manner. By analysing the effect of the widely used modulator 1,6-hexanediol, we find that the compound inhibits phase separation by acting as a solvation agent that expands polypeptide chains. Extending the strategy to in cellulo data, we even quantify the relative energetic contributions of individual proteins within complex condensates. Together, our approach provides a generic and broadly applicable tool for dissecting the forces governing biomolecular condensation and guiding the rational modulation of condensate behaviour.
@article{Ausserwöger9050,
author={Hannes Ausserwöger, Ella de Csilléry, Daoyuan Qian, Georg Krainer, Timothy J Welsh, Tomas Sneideris, Titus Franzmann, Seema Qamar, Nadia A Erkamp, Jonathan Nixon-Abell, Mrityunjoy Kar, Peter St George-Hyslop, Anthony Hyman, Simon Alberti, Rohit V Pappu, Tuomas P J Knowles},
title={Quantifying collective interactions in biomolecular phase separation.},
journal ={Nature communications},
volume={16},
issue ={1},
pages={null--null},
year=2025
}

Sakurako Tanida, Kana Fuji, Linjie Lu, Tristan Guyomar, Byung Ho Lee, Alf Honigmann, Anne Grapin-Botton, Daniel Riveline, Tetsuya Hiraiwa#, Makiko Nonomura#, Masaki Sano#
Predicting organoid morphology through a phase field model: Insights into cell division and lumenal pressure.
PLoS Comput Biol, 21(8) Art. No. e1012090 (2025)
Open Access PubMed Source   

Organoids are ideal systems to predict the phenotypes of organs. However, there is currently a lack of understanding regarding the generalized rules that enable use of simple cellular principles to make morphological predictions of entire organoids. Therefore, we employed a phase field model with the following basic components: the minimum conditions for the timing and volume of cell division, lumen nucleation rules, and lumenal pressure. Through our model, we could compute and generate a myriad of organoid phenotypes observed till date. We propose morphological indices necessary to characterize the shapes and construct phase diagrams and show their dependencies on proliferation time and lumen pressure. Additionally, we introduced the lumen-index parameter, which helped in examining the criteria to maintain organoids as spherical structures comprising a single layer of cells and enclosing an intact lumen. Finally, we predict a star-like organoid phenotype that did not undergo differentiation, suggesting that the volume constraint during cell division may determine the final phenotype. In summary, our approach provides researchers with guidelines to test the mechanisms of self-organization and predict the shape of organoid.
@article{Tanida9052,
author={Sakurako Tanida, Kana Fuji, Linjie Lu, Tristan Guyomar, Byung Ho Lee, Alf Honigmann, Anne Grapin-Botton, Daniel Riveline, Tetsuya Hiraiwa, Makiko Nonomura, Masaki Sano},
title={Predicting organoid morphology through a phase field model: Insights into cell division and lumenal pressure.},
journal ={PLoS computational biology},
volume={21},
issue ={8},
pages={null--null},
year=2025
}
* joint first authors, # joint corresponding authors