bims-ecemfi 2026-05-31 papers

bims-ecemfi

Biomed News

on ECM and fibroblasts

Issue of 2026–05–31
thirteen papers selected by
Badri Narayanan Narasimhan, University of California, San Diego

Traction Force Microscopy for Viscoelastic Substrates: A Semi-Analytical Method.
Matrix Mechanics Governs Mechano-Metabolic Adaptation across Cancer Grades in Bladder Spheroids.
Quantitative analysis of fibroblast migration reveals migratory states characterized by force generation, cell shape and motion.
Composition Matters: Collagen vs Polyacrylamide Modulates Distinct Trabecular Meshwork Cell Traction.
Identifying Mechano-Modulators of Myometrial Contractility in a Scalable Hydrogel Culture Platform.
Force loading on molecular clutches governs the stability of cell lamellipodia.
Assembly and remodeling of collagen and elastic fibers in pathophysiology: Proteases have the final cut.
Instant fluorescence lifetime imaging microscopy reveals mechano-metabolic reprogramming of stromal cells in breast peritumor microenvironment.
Computational models in directed cell migration.
Amoeboid cancer cells at a glance.
Mapping cellular and ECM heterogeneity in pulmonary fibrosis - insights from recent spatiomics studies.
Extrinsic MMPs drive epithelial shape change via basal extracellular matrix disassembly in the Drosophila wing disc.
ECMSim: A high-performance interactive web application for real-time spatiotemporal simulation of cardiac ECM signaling and diffusion.

Adv Sci (Weinh). 2026 May 28. e22252

Traction Force Microscopy for Viscoelastic Substrates: A Semi-Analytical Method.

Adrià Villacrosa-Ribas, Daniëlle C A Duffhues, Pim van den Bersselaar, Sarah Pragnere, Bart G W Groenen, Mariana Azevedo Gonzalez Oliva, Giuseppe Ciccone, Manuel Salmeron-Sanchez, Carlijn V C Bouten, Jose J Muñoz, Vito Conte.

  Traction force microscopy (TFM) quantifies cellular forces at the cell-extracellular matrix interface, yet elastic formulations neglect viscous dissipation and can misinterpret cellular forces on viscoelastic substrates. We introduce a semi-analytical 2D viscoelastic TFM (veTFM) that generalizes the Boussinesq framework of elastic TFM to Generalized Maxwell (GMX) substrates with one or two components. By combining Fourier and Laplace transforms, veTFM quantifies time-resolved tractions in finite-thickness substrates and resolves stress-free reference and substrate pre-stress. We derive criteria for when elastic regimes remain valid in this framework. This positions veTFM as a scalable extension of standard 2D TFM (eTFM) to viscoelastic substrates, identifying when eTFM remains sufficient, which elastic limit applies, and when full viscoelastic quantification is required. Applied to beating cardiomyocytes, epithelial cells, and dermal fibroblasts cultured on linear-polyacrylamide and alginate viscoelastic hydrogels, veTFM shows that the elastic or viscoelastic regime engaged by the cell depends on timescale matching between the loading rate and the substrate's relaxation times. Notably, for the Generalized Maxwell substrates analyzed here, viscoelastic traction magnitudes scale with the substrate's total dissipation rather than individual relaxation times, with total dissipation setting traction magnitude and timescale matching determining whether the cell engages the substrate in an elastic or viscoelastic regime.

Keywords:  cell–material interactions; semi‐analytical methods; stress relaxation; viscoelastic hydrogels; viscoelastic traction force microscopy

DOI:  https://doi.org/10.1002/advs.202522252
ACS Appl Mater Interfaces. 2026 May 27.

Matrix Mechanics Governs Mechano-Metabolic Adaptation across Cancer Grades in Bladder Spheroids.

Sara Metwally, Dorota Gil, Justyna Śmiałek-Bartyzel, Joanna Pabijan, Gracjan Wątor, Kajangi Gnanachandran, Massimiliano Berardi, Łukasz Kozłowski, Navdeep, Małgorzata Lekka.

  Extracellular matrix (ECM) mechanics is pivotal regulators of tumor progression, yet how viscoelasticity and matrix architecture converge to shape metabolic and invasive adaptation remains insufficiently defined. We postulate that mechanical stimuli from the ECM induce coordinated changes in adhesive and metabolic pathways, and that the nature of this independent mechano-metabolic pathway is conserved across benign, low-invasive, and high-invasive bladder cancer phenotypes. Therefore, we engineered collagen-hyaluronan hydrogels with tunable stiffness to recapitulate soft and rigid tumor microenvironments and profiled bladder cancer spheroids representing benign, low-invasive, and highly invasive states. Integrating hydraulic force spectroscopy, rheology, and molecular phenotyping, we show that matrix stiffening differentially reprograms spheroid architecture, motility, and adhesion- and metabolism-related gene expression. Spheroid behavior emerged from the interplay between intrinsic mechanical properties, matrix rheology, and molecular adaptation. HCV29 spheroids formed rigid, compact structures, relying on cell-matrix adhesion rather than metabolic or proteolytic remodeling. HT1376 spheroids activated glycolysis (HK2) and MMP-2-dependent ECM remodeling in soft matrices, but remained largely nonmigratory, indicating decoupling of invasive priming from motility. T24 spheroids were soft, deformable, and highly migratory in compliant matrices, integrating metabolic reprogramming, adhesion remodeling (E-/N-cadherin, SDC4), and radial collagen fiber alignment to drive invasion. Notably, canonical FAK/AKT/mTOR signaling was absent across all spheroids, while pS6 ribosomal protein and ILK indicated noncanonical, SDC4/integrin-ILK-dependent mechanotransduction supporting cytoskeletal dynamics, metabolism, and ECM remodeling. Collagen organization further differed across spheroid types, with dense, radially aligned fibers in HT1376, intermediate architecture in HCV29, and loose, disorganized networks in T24, closely matching their distinct migratory behaviors and cell-ECM interactions. These findings reveal stage-specific mechanometabolic strategies in bladder cancer, demonstrating how ECM mechanics and architecture jointly guide invasion, metabolic adaptation, and local immune modulation, including the regulation of immune cell infiltration and tumor immune evasion.

Keywords:  bladder cancer; extracellular matrix mechanics; hydrogel model; mechanotransduction; tumor microenvironment

DOI:  https://doi.org/10.1021/acsami.5c25973
bioRxiv. 2026 May 11. pii: 2026.05.06.723282. [Epub ahead of print]

Quantitative analysis of fibroblast migration reveals migratory states characterized by force generation, cell shape and motion.

Elizabeth M Davis, Max A Hockenberry, Harrison H Truscott, Noah J Shaul, James E Bear, Timothy C Elston.

Cell migration depends on coordinating cell shape changes with force generation, yet how these processes are integrated remains unclear. Here, we combine live-cell imaging with traction force microscopy and computational analysis to quantify cell morphology, motility and force generation in migrating fibroblasts. We find that traction force magnitudes display a multimodal distribution, suggesting discrete migratory regimes. Using a Hidden Markov Model, we identify distinct force states that exhibit differences in shape and motion metrics, and show that individual cells transition between force states over time. To test the role of cytoskeletal organization in establishing the identified states, we analyzed cells lacking Arpc 2, which disrupts branched actin assembly. Despite reduced forces and altered morphology, these cells also exhibit three migratory states. State transitions occur more frequently in cells lacking Arpc2 and unlike normal cells their protrusion geometry is force dependent. Together, our findings show that cell migration is organized into discrete mechanical states that couple morphology, motility and force generation.
SUMMARY STATEMENT: Fibroblast motility involves distinct migratory states. These states exist independent of branched actin. However, state transition frequencies, traction force magnitudes and protrusion geometry are branched actin dependent.

DOI: https://doi.org/10.64898/2026.05.06.723282
ACS Biomater Sci Eng. 2026 May 29.

Composition Matters: Collagen vs Polyacrylamide Modulates Distinct Trabecular Meshwork Cell Traction.

Alireza Karimi, Hasti Golchin, Ansel Stanik, Megan Adamec, Mini Aga, Elizabeth White, Mary Kelley, Ted Acott.

  Cells actively sense not only substrate stiffness but also matrix architecture and composition. To understand how these factors play a role in mechanobiology while minimizing stiffness as a dominant variable, we cultured normal high-flow human trabecular meshwork (TM) cells on a fibrous type I collagen gel and a collagen-coated polyacrylamide (PAM) gel (nominal stiffness ∼4.7 kPa for PAM; collagen fiber stiffness characterized by atomic force microscopy (AFM)) but with distinct microstructures, including a fibrous, elastic/viscoelastic type I collagen gel and an amorphous, linearly/non-linearly elastic polyacrylamide (PAM) gel. Using live 3D traction force microscopy and a traction-release (trypsin detachment) assay, we quantified cell-induced displacement fields and computed traction force distributions, strain, divergence (∇·u), and curl (∇ × u) on both gels. Across both gels, TM cells on collagen generated multi-fold higher tractions than on PAM throughout detachment; at 20 min, the median traction was ∼2.66 kPa (0.61-6.27 kPa) on collagen compared to ∼0.27 kPa (0.23-0.47 kPa) on PAM (∼9.8×). Median strain at 20 min was ∼1.31% (0.16-2.86) on collagen compared to ∼0.10% (0.076-0.163) on PAM (∼13×). Curl was consistently higher on collagen, i.e., 12 min medians: 4.24 compared to 0.27; ∼15×, whereas PAM remained near ∼0.3. Divergence stayed near zero on both substrates without a consistent negative shift on collagen. On collagen, traction tended to co-vary with weak divergence and higher curl over time, consistent with long-range force transmission and fiber recruitment, whereas on PAM, deformations were confined to the immediate adhesion footprint with minimal net divergence or rotation. Live confocal imaging and SEM corroborated distinct morphologies as elongated, fiber-aligned cells embedded within the 3D-like collagen network versus compact, uniformly spread cells on the planar PAM surface. Our data show that, with nominal stiffness approximately matched, switching from a collagen-coated 2D hydrogel to a fibrillar collagen matrix changes how TM cells generate, pattern, and transmit forces. These differences should be interpreted as the aggregate effect of the full matrix context rather than microstructure alone.

Keywords:  extracellular matrix; mechanobiology; polyacrylamide; trabecular meshwork; traction force microscopy; type i collagen

DOI:  https://doi.org/10.1021/acsbiomaterials.6c00588
Tissue Eng Part A. 2026 May 23. 19373341261449868

Identifying Mechano-Modulators of Myometrial Contractility in a Scalable Hydrogel Culture Platform.

Isabella C Claure, Catherine M Klapperich, Joyce Y Wong.

  Maternal and fetal health during pregnancy is closely tied to contractile modulation of the uterine myometrium, as dysfunctional contractions underlie pregnancy complications such as preterm labor and postpartum hemorrhaging. Structural abnormalities increase the risk for pregnancy complications, yet the complex interplay between biochemical and biomechanical cues in the myometrial microenvironment is not well defined. Significant gaps in our understanding of myometrial physiology and the lack of physiologically relevant research tools to enable systematic investigation have resulted in a largely ineffective and nonspecific therapeutic landscape for myometrial contractile modulation during pregnancy. We address this unmet need by developing a widely accessible approach for in vitro hydrogel platform fabrication to advance the study of agonist-mediated calcium responses in myometrial cells. We directly fabricated polyacrylamide hydrogels in polypropylene multiwell plates and Petri dishes and validated their mechanical properties and use as a mechanically tunable cell culture substrate. Using "physiological" matrix conditions during pregnancy, a fluorescent calcium mobilization assay was implemented in a plate-reader-based workflow to determine the dose sensitivity of myometrial cells to the endogenous agonist oxytocin. Using hydrogels with elastic moduli spanning physiological, pathological, and supraphysiological conditions in the myometrium, we assessed stiffness-mediated effects in myometrial cell behavior, including agonist-mediated calcium responses. We observed the mechanosensitive modulation of calcium response curve amplitude in oxytocin-stimulated myometrial cells. Myometrial cell behavior on mechanically tunable substrates was compared against widely used tissue culture plastic, and the observed changes to myometrial cell morphology and calcium responses highlight the significant influence of supraphysiological substrates. To explore complex pathological microenvironments, myometrial cells were exposed to the proinflammatory trigger lipopolysaccharide (LPS) before agonist stimulation. In our studies, LPS exposure altered calcium responses during oxytocin stimulation in cells cultured on supraphysiological substrates. Altogether, we present an easily adoptable in vitro hydrogel platform with scalable fabrication and versatile application use, including new directions in myometrial mechanobiology.Impact StatementWe investigated mechanosensitive modulation of agonist-mediated calcium responses in myometrial cells during pregnancy using a high-throughput in vitro polyacrylamide hydrogel platform. Polypropylene labware enabled scalable fabrication of an in vitro hydrogel platform without being costly or labor-intensive. Our studies found that oxytocin-stimulated calcium responses in myometrial cells are sensitive to nonphysiological matrix conditions. This work highlights the importance of using physiologically relevant engineered microenvironments and represents new directions for understanding myometrial mechanobiology. Our platform can help accelerate the identification of agonists and antagonists to counteract dysfunctional myometrial contractions and can be used more broadly in other tissues that exhibit mechanosensitive pathologies.

Keywords:  calcium mobilization; high-throughput; hydrogel; maternal health

DOI:  https://doi.org/10.1177/19373341261449868
Proc Natl Acad Sci U S A. 2026 Jun 02. 123(22): e2604349123

Force loading on molecular clutches governs the stability of cell lamellipodia.

Ruihao Xue, Lezi Kang, Yonggang Chen, Haoxiang Yang, Hongyuan Jiang, Ze Gong.

  Cells use lamellipodia, thin actin-rich membrane protrusions, to probe the mechanical properties of their microenvironment. During mechanosensing, lamellipodia often exhibit dynamic instability in the form of protrusion-retraction cycles. However, how this mechanical instability arises during mechanotransduction remains poorly understood. Here, we develop a minimal mechanochemical model for lamellipodial dynamics that integrates membrane deformation, myosin contractility, and binding kinetics of adhesion molecules (molecular clutches). Through stochastic simulations and analytical mean-field analysis, we demonstrate that both loading rate and force magnitude applied by myosin-driven retrograde flow control the clutch binding kinetics, governing lamellipodial stability and cellular mechanosensing. Specifically, a slow loading rate promotes sustained clutch engagement and traction buildup, while a high force magnitude ruptures bound clutches. Their temporal interplay gives rise to protrusion-retraction cycles in lamellipodia. Furthermore, the model predicts a biphasic response to myosin perturbation, consistent with quantitative experimental observations. Overall, the theoretical model highlights force loading as the key mechanical input driving lamellipodial instability and cellular mechanosensing, advancing our understanding of mechanotransduction during cell spreading.

Keywords:  Brownian ratchet; force loading; lamellipodium; mechanosensing; motor-clutch model

DOI:  https://doi.org/10.1073/pnas.2604349123
FEBS J. 2026 May 29.

Assembly and remodeling of collagen and elastic fibers in pathophysiology: Proteases have the final cut.

Sabrina Haddou, Alexis David, Oskar Lipinski, Rosa Doñate Puertas, Agathe Maroteaux, Carine Le Goff, Catherine Moali, Fabien Lecaille, Laurent Duca.

  The extracellular matrix (ECM) provides both architectural integrity and signaling cues to tissues, largely through its fibrous components-collagen and elastin. Collagen fibrils consist of a core of various collagen types associated with several non-collagenous binding partners and confer tensile strength to tissues, while elastic fibers, composed of cross-linked elastin on a fibrillin-rich scaffold, ensure elasticity and resilience. Far from being mere degradative enzymes, proteases are key regulators of both the assembly and turnover of these networks. Metalloproteinases of the BMP1/tolloid-like, meprin and ADAMTS families orchestrate procollagen maturation, while lysyl oxidases and related enzymes drive covalent cross-linking of collagen and elastin fibers, also under proteolytic control. Matrix metalloproteinases (MMPs) and cysteine cathepsins further modulate collagen structure and degradation, generating bioactive fragments used as clinical biomarkers. In parallel, ADAMTS and ADAMTS-like proteases orchestrate fibrillin microfibril organization, fibulin interactions, and the topography of elastogenesis. Elastolytic proteases-including cathepsins K, S, and V, as well as MMP2, MMP7, MMP9, and MMP12-mediate physiological remodeling but also fuel pathological states when dysregulated, releasing elastin-derived peptides that act as potent signaling matrikines. Genetic or acquired defects in these proteolytic pathways underlie diverse connective tissue diseases such as osteogenesis imperfecta, Ehlers-Danlos, and acromelic dysplasias, as well as fibrosis, emphysema, and vascular aging. This review integrates recent structural, biochemical, and pathological insights into how proteases coordinate collagen and elastin dynamics, highlighting novel therapeutic strategies-including substrate- and exosite-selective inhibitors-to restore ECM homeostasis while minimizing off-target effects.

Keywords:  collagen; connective tissue disorders; elastin; extracellular matrix; fiber remodeling; proteases

DOI:  https://doi.org/10.1111/febs.70608
iScience. 2026 Jun 19. 29(6): 115931

Instant fluorescence lifetime imaging microscopy reveals mechano-metabolic reprogramming of stromal cells in breast peritumor microenvironment.

Julian Najera, Hao Chen, Bianca Batista, Frank Ketchum, Aktar Ali, Pinar Zorlutuna, Scott Howard, Meenal Datta.

  The breast peritumor microenvironment (pTME) is increasingly recognized as a mediator of breast cancer progression and treatment resistance. However, how tumor compressive forces (i.e., solid stresses) influence it remains unclear. Using instant fluorescence lifetime imaging microscopy (FLIM), we show that in vitro compression metabolically reprograms stromal cells found in the breast pTME. Namely, compression shifts fibroblasts and differentiated adipocytes toward a more glycolytic state, but promotes increased oxidative phosphorylation in undifferentiated adipocytes. Through RNA-sequencing, we confirmed that compression downregulates oxidative phosphorylation and upregulates glycolysis in fibroblasts. Furthermore, we demonstrate that compression induces mitochondrial dysregulation in undifferentiated adipocytes, driven partly by upregulated mitophagy and disrupted fission/fusion dynamics. The analysis of human breast cancer samples confirms these stromal cell types recapitulate these distinct metabolic states, consistent with in vitro findings. By elucidating tumor-host mechano-metabolic interactions, these results will inform the development of innovative treatment strategies to improve survival.

Keywords:  health sciences; medicine; microenvironment; oncology

DOI:  https://doi.org/10.1016/j.isci.2026.115931
Front Cell Dev Biol. 2026 ;14 1815999

Computational models in directed cell migration.

Pablo Sáez.

  Directed cell migration is a fundamental biological process underlying development, tissue homeostasis, immune responses, and disease progression. While chemotaxis has long dominated conceptual frameworks of guidance, it is now clear that cells also respond robustly to physical cues such as mechanical stiffness gradients and electric fields. Still, how cells integrate multiple coexisting signals is poorly understood. Advances in experimental techniques have enabled precise control of these cues and revealed a rich diversity of taxis behaviors across cell types and environments. However, this experimental progress has outpaced the development of unifying theoretical frameworks capable of integrating multiple guidance modalities. In this review, we synthesize current understanding of well-known taxis, situating them within the broader landscape of physical taxis and highlighting common mechanistic themes. We discuss recent biophysical and computational models that aim to capture directed migration as an emergent property of coupled force generation, adhesion dynamics, and polarity regulation. Finally, we identify key experimental and theoretical gaps, and argue that integrated, multiscale modeling approaches are essential for moving from phenomenological descriptions toward predictive theories of cell migration in complex physiological settings.

Keywords:  cell migration modeling; cell polarity; directed cell migration; durotaxis; electrotaxis

DOI:  https://doi.org/10.3389/fcell.2026.1815999
J Cell Sci. 2026 May 15. pii: jcs264674. [Epub ahead of print]139(10):

Amoeboid cancer cells at a glance.

Ritobrata Ghose, Victoria Sanz-Moreno.

  Amoeboid behaviour represents a distinct and clinically significant cancer cell state within the epithelial-to-mesenchymal transition (EMT) spectrum. Defined by the loss of cell-cell junctions and adoption of a rounded morphology, amoeboid cancer cells exhibit low adhesion and rely heavily on Rho-ROCK-myosin II-mediated cortical contractility. This combination of high contractility and reduced adhesion enables rapid migration through dense, confining environments, using blebs as functional protrusions. This behaviour is commonly observed at tumour invasive fronts, within metastatic deposits and among therapy-resistant cell populations. Amoeboid identity integrates multiple biochemical signalling programmes alongside mechanical cues such as confinement, matrix topography and shear stress. Collectively, these factors drive a highly plastic state characterised by stem-cell-like traits, metabolic adaptability, low oxidative stress and an immunosuppressive secretome. Such features confer strong metastatic potential and broad resistance to therapy, underpinned by core physicochemical dependencies on cortical tension, membrane mechanics and redox balance. This Cell Science at a Glance article and the accompanying poster highlight these defining characteristics, establishing amoeboid behaviour as a crucial driver of cancer progression and an increasingly promising therapeutic target.

Keywords:  Amoeboid cancer cells; Cytoskeleton; Immunomodulation; Mechanobiology; Metastasis

DOI:  https://doi.org/10.1242/jcs.264674
Cell Biomater. 2026 Apr 21. pii: 100315. [Epub ahead of print]2(4):

Mapping cellular and ECM heterogeneity in pulmonary fibrosis - insights from recent spatiomics studies.

Mahsa Yazdani, Li Wang, Qiyue Ding, Negin Frazad, Mingyu Yang, Shriramprasad Venkatesan, Michal Stachowiak, Laertis Ikonomou, Ya-Wen Chen, Rong Fan, Yang Liu, Ruogang Zhao.

Idiopathic pulmonary fibrosis (IPF) features spatially heterogeneous tissue remodeling, with fibroblast foci (FF) acting as central hubs of fibrogenesis at the interface between remodeled and preserved alveolar regions. Emerging spatiomics studies reveal that FF comprise distinct functional zones-an activated fibroblast core, a transitional front, and surrounding mature fibrosis-each defined by unique cellular and molecular programs. Spatially resolved profiling has uncovered diverse fibroblast subpopulations, epithelial injury states, macrophage niches, and cell-matrix signaling circuits that together shape the fibrotic niche. By linking gene and protein expression to tissue architecture, spatiomics clarifies how fibroblast activation, epithelial remodeling, and ECM reorganization integrate across space to drive irreversible scarring. This Perspective summarizes spatiomics approaches in pulmonary fibrosis, synthesizes the key biological insights they have revealed, and highlights emerging opportunities-spanning integrative multiomics, AI-guided inference, and organoid models-to advance mechanistic understanding and therapeutic discovery in IPF.

DOI: https://doi.org/10.1016/j.celbio.2025.100315
Commun Biol. 2026 May 29.

Extrinsic MMPs drive epithelial shape change via basal extracellular matrix disassembly in the Drosophila wing disc.

Chigusa Hinata, Hirotatsu Nakagawa, Shigenori Nonaka, Katsuya Nozaki, Yoshikatsu Sato, Shizue Ohsawa.

Epithelial morphogenesis generates complex tissue architectures with remarkable reproducibility, yet how tissue-scale epithelial curvature transitions are triggered in vivo remains poorly understood. Here, we show that epithelial morphogenesis during early pupal development of the Drosophila wing disc is regulated non-autonomously through spatially restricted remodeling of the basal extracellular matrix (ECM) by neighboring tissues. Live imaging analyses reveal a previously unrecognized morphogenetic event at the larval-to-pupal stage, in which the wing disc epithelium undergoes a concave-to-convex curvature inversion. This curvature inversion is preceded by local loss of Collagen IV from the basal ECM, particularly in the notum and hinge regions. Rather than being driven autonomously by the epithelium, the shape change depends on adjacent non-epithelial cell populations, including myoblasts and tracheal cells, whose dynamic behaviors are spatially and temporally associated with basal ECM disassembly. Mechanistically, systemic ecdysone signaling activates Mmp1 and Mmp2 in these neighboring tissues, leading to localized basal ECM disassembly that permissively enables epithelial self-organization. Together, our findings identify extrinsic ECM remodeling at tissue interfaces as a non-autonomous regulatory layer that spatially licenses tissue-scale epithelial curvature transitions during development.

DOI: https://doi.org/10.1038/s42003-026-10376-9
Matrix Biol Plus. 2026 Jun;30 100195

ECMSim: A high-performance interactive web application for real-time spatiotemporal simulation of cardiac ECM signaling and diffusion.

Hasi Hays, William J Richardson.

  Extracellular matrix (ECM) remodeling is central to a wide variety of healthy and diseased tissue processes. Unfortunately, predicting ECM remodeling under various chemical and mechanical conditions has proven to be excessively challenging, due in part to its complex regulation by intracellular and extracellular molecular reaction networks that are spatially and temporally dynamic. We introduce ECMSim, which is a highly interactive, real-time, and web application designed to simulate heterogeneous matrix remodeling. The current model simulates cardiac scar tissue with configurable input conditions using a large-scale model of the cardiac fibroblast signaling network. Cardiac fibrosis is a major component of many forms of heart failure. ECMSim solves 1.37 million coupled ordinary differential equations (ODEs) and executes approximately 4.84 million operations per time step in real time, encompassing 137 molecular species and 259 regulatory interactions per cell across a 100 × 100 spatial array (10,000 cells), which accounts for inputs, receptors, intracellular signaling cascades, ECM production, feedback loops, and molecular diffusion. The algorithm is represented by a set of ODEs that are coupled with ECM molecular diffusion. The equations are solved on demand using compiled C++ and the WebAssembly standard. The platform includes brush-style cell selection to target a subset of cells with adjustable input molecule concentrations, parameter sliders to adjust parameters on demand, and multiple coupled real-time visualizations of network dynamics at multiple scales. Implementing ECMSim in standard web technologies enables a fully functional application that combines real-time simulation, visual interaction, and model editing. The software enables the investigation of pathological or experimental conditions, hypothetical scenarios, matrix remodeling, or the testing of the effects of an experimental drug(s) with a target receptor.

Keywords:  Cardiac fibrosis; Extracellular matrix; Heart failure; Matrix remodeling; ODEs; Spatial heterogeneity

DOI:  https://doi.org/10.1016/j.mbplus.2026.100195