bims-ecemfi 2026-01-18 papers

bims-ecemfi

Biomed News

on ECM and fibroblasts

Issue of 2026–01–18
seventeen papers selected by
Badri Narayanan Narasimhan, University of California, San Diego

Biophysical modeling identifies an optimal hybrid amoeboid-mesenchymal mechanism for maximal T cell migration speeds.
Glassy adhesion dynamics govern transitions between sub-diffusive and super-diffusive cancer cell migration on viscoelastic substrates.
Packing-driven mechanotransduction: local crowding overrides adhesion and stiffness cues for YAP activation in cellular collectives.
Linking molecular tension and cellular tractions: a multiscale approach to focal adhesion mechanics.
Modes of mechanical guidance of adhesion-independent cell migration.
Local mechanobiological disruption in solid tumor-driven vascular permeability: A competition between mechanical vs chemical stimuli.
Generation of In Vivo-Inspired 3D Collagen Models for Guided Tumor Invasion In Vitro.
Development of self-assembled peptide hydrogels containing matrix-metalloproteinase degradable motifs for 3D lung cancer models.
Expression of vimentin intermediate filaments in epithelial cells promotes cell migration and cell matrix interaction in 3D.
Cell-body curvature modulates stall frequency to enhance Vibrio cholerae swimming and chemotaxis through hydrogels.
Engineering bioactive fibrous constructs: Bioprinting stem cell-laden collagen-derived hydrogels with short collagen microfibers.
Genotype-Dependent Morpho-Mechanical Profiling of Patient-Derived Human Myotubes on Nanogrooved Substrates.
Protocol for orthotopic implantation of a collagen hydrogel to model pancreatic ductal adenocarcinoma in mice.
GOT1 Inhibition Induces Extracellular Matrix Remodeling in Pancreatic Cancer.
Viscoelastic stress relaxation, fast and slow.
Architecture-encoded mechanics and communication in microtubules: a multiscale computational study.
Cell surface engineering with a pseudofibrotic ECM reprograms the antifibrotic activity of mesenchymal stromal cells.

Cell Rep. 2026 Jan 12. pii: S2211-1247(25)01596-7. [Epub ahead of print]45(1): 116824

Biophysical modeling identifies an optimal hybrid amoeboid-mesenchymal mechanism for maximal T cell migration speeds.

Roberto Alonso-Matilla, Diego I Pedro, Alfonso Pepe, Jose Serrano-Velez, Michael Dunne, Duy T Nguyen, W Gregory Sawyer, Paolo P Provenzano, David J Odde.

  Despite recent advances in cell migration mechanics, the principles governing rapid T cell movement remain unclear. Efficient migration is critical for antitumoral T cells to locate and eliminate cancer cells. To investigate the upper limits of cell speed, we develop a hybrid stochastic-mean field model of bleb-based cell motility. Our model suggests that cell-matrix adhesion-free bleb migration is highly inefficient, challenging the feasibility of adhesion-independent migration as a primary fast mode. Instead, we show that T cells can achieve rapid migration by combining bleb formation with adhesion-based forces. Supporting our predictions, three-dimensional gel experiments confirm that T cells migrate significantly faster under adherent conditions than in adhesion-free environments. These findings highlight the mechanical constraints of T cell motility and suggest that controlled modulation of tissue adhesion could enhance immune cell infiltration into tumors. Our work provides insights into optimizing T cell-based immunotherapies and underscores that indiscriminate antifibrotic treatments may hinder infiltration.

Keywords:  CP: cell biology; actomyosin contractility; amoeboid; biophysical model; bleb; cell migration

DOI:  https://doi.org/10.1016/j.celrep.2025.116824
Nat Commun. 2026 Jan 13.

Glassy adhesion dynamics govern transitions between sub-diffusive and super-diffusive cancer cell migration on viscoelastic substrates.

Vivek Sharma, Kolade Adebowale, Ze Gong, Ovijit Chaudhuri, Vivek B Shenoy.

Cell migration is pivotal in cancer metastasis, where cells navigate the extracellular matrix (ECM) and invade distant tissues. While the ECM is viscoelastic, exhibiting time-dependent stress relaxation, its influence on cell migration remains poorly understood. Here, we employ an integrated experimental and modeling approach to investigate filopodial cancer cell migration on viscoelastic substrates and uncover a striking transition from sub-diffusive to super-diffusive behavior driven by the substrate's viscous relaxation timescale. Conventional motor-clutch based migration models fail to capture these anomalous migration modes, as they overlook the complex adhesion dynamics shaped by broad distribution of adhesion lifetimes. To address this, we develop a glassy motor-clutch model that incorporates the rugged energy landscape of adhesion clusters, where multiple metastable states yield long-tailed adhesion timescales. Our model reveals that migration dynamics are governed by the interplay between cellular and substrate timescales: slow-relaxing substrates prolong trapping, leading to sub-diffusion, while fast-relaxing substrates promote larger steps limiting trapping, leading to super-diffusion. Additionally, we uncover the role of actin polymerization and contractility in modulating adhesion dynamics and driving anomalous migration. These findings establish a mechanistic framework linking substrate viscoelasticity to cell motility, with implications for metastasis and cancer progression.

DOI: https://doi.org/10.1038/s41467-025-67709-1
J R Soc Interface. 2025 Dec 17. pii: 20250490. [Epub ahead of print]22(233):

Packing-driven mechanotransduction: local crowding overrides adhesion and stiffness cues for YAP activation in cellular collectives.

Valeriia Grudtsyna, Vinay S Swaminathan, Amin Doostmohammadi.

  The regulation of mechanotransduction is crucial for various cellular processes, including stem cell differentiation, wound healing and cancer progression. While the activation of mechanotransduction has been extensively studied in single cells, it remains unclear whether similar mechanisms extend to mechanotransduction in multicellular collectives. Here, by focusing on Yes-associated protein (YAP), known as the master regulator of mechanotransduction, we reveal that the local packing fraction of cells acts as the primary determinant of YAP activation in cell collectives. We further show that local packing fraction modulates the isotropic stress landscape, with sparse regions experiencing large stress fluctuations and dense regions displaying stress equilibration. Remarkably, this packing fraction-dependent regulation persists even under conditions of disrupted force transmission through cell-cell and cell-substrate adhesion, suggesting a robust and conserved relation between YAP activation and local packing fraction in cell collectives. In particular, we show that local packing fraction-dependent activation of YAP in cell collectives is independent of substrate stiffness, E-cadherin expression and myosin contractility, in stark contrast to YAP activation in single cells. Our results thus offer a new perspective on mechanotransduction, highlighting the critical role of the local packing fraction of cells in dictating YAP dynamics within multicellular contexts. These insights have significant implications for tissue engineering and understanding tumour microenvironments, where cellular heterogeneity often drives functional outcomes.

Keywords:  E-cadherin; Yes-associated protein; actin cytoskeleton; collective mechanotransduction; local packing fraction; nuclear shape; substrate stiffness

DOI:  https://doi.org/10.1098/rsif.2025.0490
Commun Biol. 2026 Jan 12.

Linking molecular tension and cellular tractions: a multiscale approach to focal adhesion mechanics.

Samet Aytekin, Laurens Kimps, Quinten Coucke, Débora Linhares, Sarah Vorsselmans, Swaraj Deodhar, Ruth Cardinaels, Mar Cóndor, Jorge Barrasa-Fano, Hans Van Oosterwyck, Susana Rocha.

Focal adhesions (FAs) are mechanosensitive structures that mediate force transmission between cells and the extracellular matrix. While Traction Force Microscopy (TFM) quantifies cellular tractions exerted on deformable substrates, Förster Resonance Energy Transfer (FRET)-based tension probes, such as vinculin tension sensors, measure molecular-scale forces within FA proteins. Despite their potential synergy, these methods have rarely been combined to explore the interplay between molecular tension and cellular tractions. Here, we introduce a framework integrating TFM and FRET-based vinculin tension sensors to investigate FA mechanics across scales. At cell level, tractions and vinculin tension increased with substrate stiffness. At FA level, vinculin tension correlated solely with vinculin density, while tractions scaled with FA area, orientation, total vinculin content and vinculin density. Direct comparison of tractions to vinculin tension revealed a complex, heterogenous relationship between these forces, possibly linked to diverse cell and FA maturation states. Sub-FA analysis revealed conserved spatial patterns, with both tension and traction increasing towards the cell periphery. This multiscale approach provides an integrated workflow for studying focal adhesion forces, helping to bridge the gap between vinculin tension and cellular tractions.

DOI: https://doi.org/10.1038/s42003-026-09514-0
Soft Matter. 2026 Jan 12.

Modes of mechanical guidance of adhesion-independent cell migration.

Hanna Luise Gertack, Peter A E Hampshire, Claudia Wohlgemuth, Ricard Alert, Sebastian Aland.

Adhesion-independent migration is a prominent mode of cell motility in confined environments, yet the physical principles that guide such movement remain incompletely understood. We present a phase-field model for simulating the motility of deformable, non-adherent cells driven by contractile surface instabilities of the cell cortex. This model couples surface and bulk hydrodynamics, accommodates large shape deformations and incorporates a diffusible contraction-generating molecule (myosin) that drives cortical flows. These capabilities enable a systematic exploration of how mechanical cues direct cell polarization and migration. We first demonstrate that spontaneous symmetry breaking of cortical activity can lead to persistent and directed movement in channels. We then investigate how various physical cues - including gradients in friction, viscosity, and channel width as well as external flows and hydrodynamic interactions between cells - steer migration. Our results show that active surface dynamics can generate stimulus-specific cell behaviors, such as migration up friction gradients or escape from narrow regions. Beyond cell migration, the model offers a versatile platform for exploring the mechanics of active surfaces in biological systems.

DOI: https://doi.org/10.1039/d5sm00960j
Acta Biomater. 2026 Jan 08. pii: S1742-7061(26)00024-3. [Epub ahead of print]

Local mechanobiological disruption in solid tumor-driven vascular permeability: A competition between mechanical vs chemical stimuli.

Alejandro Martín-Contreras, María Sarasquete-Martínez, José Manuel García-Aznar, Alejandra González-Loyola, María José Gómez-Benito.

  The tumor microenvironment imposes complex biochemical and biomechanical constraints on microvasculature, contributing to aberrant tumor blood vessels, characterized by abnormal endothelial proliferation, disrupted cell-to-cell junctions and increased permeability. While vascular normalization strategies have traditionally focused on biochemical modulation, the role of mechanical forces in endothelial dysfunction remains unclear. Here, we used a microfluidic platform to dissect the mechanobiological impact of two distinct solid tumor models -pancreatic ductal adenocarcinoma (PANC-1) and lung adenocarcinoma (A549)-on three-dimensional embedded endothelial vessels. Our findings reveal that PANC-1 spheroids exert significant mechanical forces, expanding vessel diameter and disrupting endothelial barrier integrity via cellular contractility. Conversely, A549 spheroids contribute to vascular destabilization through biochemical modulation, primarily via extracellular matrix degradation and inflammatory secretomes, leading to an altered and heterogeneous endothelial permeability. Proteomic analysis of both tumor cell lines highlights distinct pathways involved in endothelial remodeling: cytoskeletal alterations and consequent stresses in pancreatic ductal adenocarcinoma, while extracellular matrix remodeling and pro-inflammatory microenvironment are found in lung adenocarcinoma. These insights underscore the necessity of tumor-specific vascular normalization strategies, combining mechanobiological and biochemical approaches to restore endothelial barrier function. Our locally controlled microfluidic approach provides a versatile platform for evaluating innovative therapeutic strategies targeting tumor-specific vasculature. STATEMENT OF SIGNIFICANCE: This study highlights the often-overlooked role of tumor-derived mechanical forces in vascular dysfunction. Within the tumor microenvironment, different tumor types disrupt the endothelial barrier through distinct, tumor-specific mechanisms, leading to varied patterns of vessel instability. Using confocal microscopy, we achieved spatially resolved analysis of local endothelial barrier damage, distinguishing focal from diffuse permeability changes. A 3D microfluidic platform was developed to replicate tumor endothelium interactions, combining live imaging, morphometric and biochemical assays, and proteomic profiling. This integrative model offers a versatile tool for evaluating drug responses under controlled mechanochemical conditions, supporting the development of personalized vascular-targeted therapies.

Keywords:  Endothelial barrier; Mechanobiology; Tumor microenvironment; Vascular dysfunction; Vessel-on-a-chip

DOI:  https://doi.org/10.1016/j.actbio.2026.01.013
Curr Protoc. 2026 Jan;6(1): e70280

Generation of In Vivo-Inspired 3D Collagen Models for Guided Tumor Invasion In Vitro.

Stijn den Daas, Gert-Jan Bakker, Diede van Ens, Eleni-Andria Grosu, Manon Vullings, Lianne Beunk, Peter Friedl, Katarina Wolf.

  Porous collagen hydrogels are widely used to model dynamic cell-extracellular matrix (ECM) interactions relevant to inflammation, wound healing, and cancer invasion. To improve the physiological relevance of such assays, it is essential to incorporate architectural ECM characteristics identified in vivo that may affect the mechanical and molecular mechanisms of cell migration, including ECM geometry, alignment, and dimensionality. We present detailed, step-by-step protocols for generating three collagen-hydrogel-based migration assays that integrate structural guidance cues, either as cleft-like deformable gaps or tunnel-like tracks, including track generation by multiphoton (MP) laser ablation. For this application, practical guidance on laser setup and integration in commonly used MP microscopes is provided. We include example applications to compare the migratory behavior of HT1080 fibrosarcoma cells, applied both as single-cell suspensions and as pre-formed spheroids, in these spatially controlled models. The data indicate that migration efficiency increases with the presence of guidance cues, highlighting the importance of such cues for modeling invasive cell behavior in 3D. These protocols provide a standardized yet adaptable framework for researchers studying ECM-guided cell migration and evaluating therapeutic strategies that target cell motility. © 2026 The Author(s). Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Under-collagen assay Basic Protocol 2: 3D interface assay Basic Protocol 3: 3D tissue track assay Support Protocol 1: Imaging of guidance models by confocal microscopy Support Protocol 2: Excitation beam adjustment Support Protocol 3: Generation of stacks of long tracks by three common microscope types.

Keywords:  cell migration; collagen hydrogel; guidance models; multiphoton microscopy; track generation by laser ablation

DOI:  https://doi.org/10.1002/cpz1.70280
Soft Matter. 2026 Jan 12.

Development of self-assembled peptide hydrogels containing matrix-metalloproteinase degradable motifs for 3D lung cancer models.

Burcu Sırma Tarım, Sedef Tamburacı, Ayben Top.

Hydrogel-forming peptides, including matrix metalloproteinase (MMP)-degradable motifs, have been employed to investigate cell-extracellular matrix interactions in vitro. However, their potential in 3D cancer models has been explored only in a few studies. In this study, we used modified MMP-2 degradable motifs (VSLRA or ASLRA) in the design of EDP1 (RVSLRADARVSLRADA) and EDP2 (RASLRADARASLRADA) peptide hydrogelators. The peptides self-assembled into nanofibrillar hydrogels with storage moduli between ∼300 and ∼400 Pa. MMP-2 degradation properties of the peptides were confirmed, and a slightly higher MMP-2 responsiveness of the EDP1 hydrogel was observed. The hydrogels were used in the encapsulation of A549 lung adenocarcinoma cancer cells and MRC-5 human lung fibroblast cells. The designed hydrogels supported the proliferation of these cells with high viability and induced cluster formation of encapsulated A549 cells similar to that observed with the RADA hydrogel. However, the hydrogel network structure affected the morphology of the migrated cells in the absence of curcumin. The addition of curcumin decreased the migration and invasion of A549 cells, resulting in a round cell morphology independent of the hydrogel matrices. Anticancer drug tests indicated that cell viability after drug treatment was higher in the 3D hydrogels than in 2D cultures. It was also confirmed that the combinational therapy of doxorubicin and curcumin decreased the cell proliferation and colonization to a greater extent compared to doxorubicin monotherapy. Thus, the hydrogels developed in this study can be used for 3D cancer models or other tissue engineering applications as an alternative to the RADA hydrogel by exploiting the MMP-2 degradation properties.

DOI: https://doi.org/10.1039/d5sm00890e
Biophys J. 2026 Jan 15. pii: S0006-3495(26)00037-8. [Epub ahead of print]

Expression of vimentin intermediate filaments in epithelial cells promotes cell migration and cell matrix interaction in 3D.

Camille Rodriguez, Hyuntae Jeong, Jiwon Kim, Lily A Cordner, Paul Cao, Suganya Sivagurunathan, Stephen A Adam, Robert D Goldman, Ian Y Wong, Ming Guo.

During a variety of physiological and pathological processes, such as development, wound healing, and tumor progression, epithelial cells collectively invade into their surroundings. Vimentin intermediate filaments (VIFs) are often observed to play a role in the epithelial cells located at the margins of 2D cultures. However, their role in 3D collective cell behavior remains underexplored. Here, we investigate how induced vimentin expression affects 3D multicellular architecture and mechanics in luminal breast cancer cells (MCF-7) that ordinarily express keratin intermediate filaments only. We find that vimentin expression significantly alters 3D cell cluster morphology, inducing protrusions and increasing boundary fluctuations. Furthermore, cells in vimentin-expressing clusters show enhanced, more stochastic migration. In addition, these clusters exert stronger and localized traction forces on the surrounding matrix, indicating increased cell-matrix interactions. Transcriptomic analysis corroborates these biophysical findings, revealing upregulated gene expression for cell migration and matrix adhesion, and downregulated cell-cell adhesion genes. Our results demonstrate that VIFs are critical in modulating 3D multicellular collective morphology and dynamics, promoting invasive-like behavior by enhancing cell migration and cell-matrix interactions. These results provide fundamental insights into understanding tissue morphogenesis and disease progression.

DOI: https://doi.org/10.1016/j.bpj.2026.01.022
bioRxiv. 2026 Jan 11. pii: 2026.01.11.698873. [Epub ahead of print]

Cell-body curvature modulates stall frequency to enhance Vibrio cholerae swimming and chemotaxis through hydrogels.

Marwan Malik, Ziyang Chen, Andrew G T Pyo, Zemer Gitai, Ned S Wingreen, Marianne Grognot.

The swimming motility of Vibrio cholerae is a virulence factor that aids in breaching the mucus layer of the small intestine. V. cholerae cells have a curved cell shape and previous work demonstrated that loss of curvature decreases infectivity. Here we investigate the mechanism by which V. cholerae 's curvature affects single-cell motility within mucus-mimicking environments. Using a multiscale chemotaxis assay, we compared the chemotactic performance of wild-type curved cells (O1 El Tor C6706) and straight mutants under linear chemical gradients in liquid solutions, viscous solutions, and soft agar hydrogels. Our findings reveal that curved and straight V. cholerae exhibit similar swimming properties in liquid and purely viscous solutions but significantly differ in hydrogels, with curved cells demonstrating an 86% increase in average chemotactic drift compared to straight mutants in the same chemical gradients. Trajectory analysis indicates that swimming speeds are comparable, but straight mutants experience more frequent stalls, reducing the total time spent swimming. We also found that stalls further reduce chemotactic performances by imposing an average reorientation of bacteria down the chemical gradient, regardless of cell shape. In-silico coarse-grained molecular dynamics simulations corroborate these results and extend them over the wide range of intestinal mucus hydrogel stiffnesses. This model also identifies an optimal curvature for enhanced movement through hydrogel-like meshes that is close to the real median curvature of the pathogen. Our findings thus highlight the mechanisms underpinning cell shape's role in V. cholerae 's pathogenicity and underscore the necessity of studying bacterial behaviors under conditions that simulate host environments.

DOI: https://doi.org/10.64898/2026.01.11.698873
Biomaterials. 2025 Dec 29. pii: S0142-9612(25)00885-3. [Epub ahead of print]329 123965

Engineering bioactive fibrous constructs: Bioprinting stem cell-laden collagen-derived hydrogels with short collagen microfibers.

Hongjuan Weng, Monize C Decarli, Wen Chen, Katrien V Bernaerts, Lorenzo Moroni.

  Natural hydrogels (e.g., collagen hydrogels) show good potential in understanding cell-matrix interaction and find application in tissue engineering. However, it remains challenging to bioprint cell-laden natural hydrogels with good printability, shape retention and stability. In this study, non-water-soluble short collagen type I microfibers (COL-I μFiber) were blended with water-soluble methacrylated collagen peptide (COPMA) and xanthan gum (XG), forming an interpenetrated network, and bioprinted into stable natural-derived COPMA-μFiber-XG constructs, followed by in situ stem cell proliferation and differentiation. First, to enhance the printability and the mechanical properties of COPMA, a COPMA-μFiber-XG bioink was developed, featuring rapid UV-curing and self-healing properties. The encapsulated human mesenchymal stem cells (hMSCs) spread along the COL-I μFibers in the bioprinted constructs, with increased metabolic activity and production of extracellular matrix and bioactive proteins (COL-I and scleraxis) in 28 days. The internal biophysical and biochemical signals provided by COL-I μFibers and the fibrous COPMA matrix synergistically interacted with exogenous biochemical signals (e.g., transforming growth factor-beta 3) to further promote stem cell differentiation. Overall, bioprinted fibrous COPMA-μFiber-XG constructs are biocompatible and bioactive matrices to support hMSCs proliferation and differentiation.

Keywords:  Bioprinting; Collagen type I microfibers; Collagen-derived hydrogels; Methacrylated collagen peptides; Xanthan gum

DOI:  https://doi.org/10.1016/j.biomaterials.2025.123965
Small. 2026 Jan 12. e11234

Genotype-Dependent Morpho-Mechanical Profiling of Patient-Derived Human Myotubes on Nanogrooved Substrates.

Raphaël Crépin, Anissa Aït Ouailal, Pierre Joanne, Onnik Agbulut, Vincent Mouly, Olek Maciejak, Michel Malo, Juan Pelta, Clément Campillo, Sid Labdi, Guillaume Lamour.

  Muscle disorders such as myofibrillar myopathies and Duchenne muscular dystrophy involve mutations in key cytoskeletal proteins and lead to progressive muscle degeneration. Yet, the mechanical characterization of affected muscle cells has relied mainly on immature or non-human models. Here, we introduce a human in vitro platform based on patient-derived immortalized myoblasts differentiated into myotubes on nanogrooved substrates, which promote alignment and organotypic maturation. Using immunostaining and atomic force microscopy (AFM), we show that desmin- and dystrophin-mutated myotubes exhibit distinct morphological and mechanical phenotypes compared to wild-type myotubes. We developed an AFM stiffness pipeline to quantify cell body stiffness across myotubes of variable thickness. Desmin- and dystrophin-mutated myotubes are stiffer than controls, with desmin mutants also displaying cytoskeletal disorganization. A dynamic fatigue assay (cyclic AFM indentations over time) further revealed impaired stiffening and faster mechanical fatigue in desmin mutants, while dystrophin mutants preserved resilience. This set of results establishes a reproducible and human-relevant system to probe muscle mechanics in disease, offering a unique intermediate model between conventional immortalized lines and complex iPSC-derived tissues, and enabling future quantitative screening and translational applications.

Keywords:  atomic force microscopy (AFM); duchenne muscular dystrophy (DMD); human muscle cell model; myofibrillar myopathies; myotube biomechanics

DOI:  https://doi.org/10.1002/smll.202511234
STAR Protoc. 2026 Jan 13. pii: S2666-1667(25)00743-9. [Epub ahead of print]7(1): 104337

Protocol for orthotopic implantation of a collagen hydrogel to model pancreatic ductal adenocarcinoma in mice.

James P Agolia, Peter Y Xie, Maria Korah, Mahsa Fallah, Rosyli F Reveron-Thornton, Chuner Guo, Biren Reddy, Rithanya Sivasubramanian, Michael T Longaker, Ovijit Chaudhuri, Deshka S Foster, Daniel Delitto.

  Available mouse models for pancreatic ductal adenocarcinoma (PDAC) are limited by slow tumor development and failure to recapitulate key stromal and immune characteristics. Here, we present a protocol for generating a collagen hydrogel mouse model for orthotopic PDAC. We describe steps for embedding mouse pancreatic cancer cells in a dense collagen hydrogel and surgically implanting it into the mouse pancreas. Mouse PDAC tumors typically reach 1 cm in diameter by 10 days after implantation and show immune and stromal cell recruitment. For complete details on the use and execution of this protocol, please refer to Korah et al.1.

Keywords:  Cancer; Cell biology; Cell culture; Model organisms

DOI:  https://doi.org/10.1016/j.xpro.2025.104337
Adv Sci (Weinh). 2026 Jan 12. e16578

GOT1 Inhibition Induces Extracellular Matrix Remodeling in Pancreatic Cancer.

Rodrigo Curvello, Sandra Hauser, Michael Seifert, Christopher K Barlow, Joel R Steele, Emma Salisbury, Daniel Croagh, Kathryn S Stok, Anna V Taubenberger, Ralf B Schittenhelm, Daniela Loessner.

  Pancreatic cancer cells rely on glutamine to sustain their survival in the stiff and poorly vascularized tumor microenvironment (TME). Inhibiting glutamic-oxaloacetic transaminase 1 (GOT1) is a strategy to target glutamine metabolism and impair cancer cell functions. However, it remains unclear how cellular and extracellular elements of the TME respond to GOT1 inhibition. We engineered a pancreatic TME model 'on a dish' and recreated the metabolic interactions. Stromal cells remodeled the extracellular matrix and upregulated metabolic programs, including glutamine metabolism, oxidative phosphorylation, and central carbon metabolism. Cell responses to GOT1 inhibition were modulated by TME elements, with reductions in cell viability and proliferation occurring only under tissue-like conditions. GOT1 inhibition altered matrix organization by upregulating different matrix-related proteins, while it did not enhance cell responses to cytotoxic drugs. Our findings uncover the metabolic crosstalk within the TME and show that metabolism-targeting treatments directly impact stromal elements of pancreatic cancer.

Keywords:  extracellular matrix; metabolism; pancreatic cancer; stromal cells; tissue engineering

DOI:  https://doi.org/10.1002/advs.202516578
Soft Matter. 2026 Jan 13.

Viscoelastic stress relaxation, fast and slow.

H Henning Winter.

Soft materials such as colloids, pastes, and polymer liquids are defined rheologically by how they build and relax stress during flow and deformation. Their internal connectivity manifests in a broad spectrum of viscoelastic eigenmodes, with relaxation ranging from fast to slow and contributions that vary from weak to strong. The interplay of these modes determines how the material deforms under shear, compression, or stretching across different processing timescales. Traditional measures of viscoelasticity, such as the Deborah number (De) and the Weissenberg number (Wi), condense this complexity into single scalar values. While useful for certain purposes, these scalar measures mask the fast/slow interplay of relaxation processes that shape the distinct responses of soft matter. To overcome this limitation, we introduce the "spectral classification of processes and eigenmodes" (SCOPE) framework. SCOPE explicitly accounts for the distributed nature of both process times and material relaxation times. It generalizes the classical De and Wi into their functional counterparts-the Deborah function and the Weissenberg function-which connect applied stress and strain to the full spectrum of relaxation times (0 < τ < τmax), thereby covering the entire range of process timescales and types of deformation. By doing so, SCOPE provides a spectral perspective on viscoelasticity that integrates fast and slow dynamics within a single, unified rheological framework. SCOPE provides criteria that separate viscous from elastic eigenmodes, and modes below or above the onset of nonlinearity. In what follows, we introduce the SCOPE framework in detail and demonstrate its functions for viscoelastic liquids.

DOI: https://doi.org/10.1039/d5sm01008j
J R Soc Interface. 2025 Dec 01. pii: 20250556. [Epub ahead of print]22(233):

Architecture-encoded mechanics and communication in microtubules: a multiscale computational study.

Eric Adriano Zizzi, Marco Cannariato, Marcello Miceli, Umberto Morbiducci, Marco Agostino Deriu.

  The mechanical architecture of microtubules (MTs) is crucial for modulating their functions within cells; however, the effect of varying the number of protofilaments (PFs) on the propagation of mechanical signals remains largely unexplored. Nevertheless, MTs assembled in vitro exhibit diverse PF numbers depending on the specific tubulin composition, stabilizing agents and cellular context, suggesting a regulated architectural adaptation. Here, we performed a multiscale computational study integrating molecular dynamics, dynamical network analysis and elastic network modelling to investigate the influence of the MT architecture on structural communication and mechanics. Our results highlight that an increase in PF number alters tubulin-tubulin contact patterns, reshapes lateral surface hydrophobicity and modulates the dynamics of a specific unstructured region known as the M-loop. Remarkably, we identified a correlation between the PF number, vibrational path length and bending stiffness, revealing that MTs with larger architectures propagate mechanical information less efficiently, but offer increased structural support. These findings suggest that MT architecture may serve as a design parameter influencing the propagation of mechanical signals across scales. Moreover, they may contribute to the emerging field of neuromechanobiology, where MTs are considered potential integrators of mechanical and informational processes within neurons.

Keywords:  Elastic Network Modelling; cytoskeleton mechanics; microtubules; molecular dynamics; protein network modelling; protofilaments

DOI:  https://doi.org/10.1098/rsif.2025.0556
Sci Adv. 2026 Jan 16. 12(3): eaea0998

Cell surface engineering with a pseudofibrotic ECM reprograms the antifibrotic activity of mesenchymal stromal cells.

Xianghua Zhong, Xinchao Liu, Jiajia Luo, Xinyang Liu, Xueting Wei, Xi Peng, Lu Wang, Huaimin Wang, Kunyu Zhang, Liming Bian, Peng Shi.

Fibrotic diseases, which impair tissue function and contribute to organ failure, remain a major clinical challenge with limited treatment options. Mesenchymal stromal cells (MSCs) offer promise for antifibrotic therapy via paracrine signaling, but their clinical efficacy is hindered by poor survival and limited functional activity after transplantation. Here, we present a cell surface engineering strategy that reprograms the antifibrotic function of MSCs by constructing a pseudofibrotic extracellular matrix (ECM) on their surface. Through in situ self-assembly of peptide-modified hyaluronic acid, we generate a nanofiber-based matrix that mimics the dense, disordered architecture of fibrotic ECM. This matrix activates the Piezo1/PI3K-Akt signaling pathway, inducing up-regulation of Mmp13-a key collagen-degrading matrix metalloproteinase-in engineered MSCs. In a rat model of myocardial infarction-associated fibrosis, engineered MSCs exhibit robust antifibrotic activity compared to unmodified MSCs. These findings establish a bioinspired strategy for MSC reprogramming and offer a path toward more effective cell-based therapies for fibrotic disease.

DOI: https://doi.org/10.1126/sciadv.aea0998