bims-ecemfi 2026-06-21 papers

bims-ecemfi

Biomed News

on ECM and fibroblasts

Issue of 2026–06–21
eight papers selected by
Badri Narayanan Narasimhan, University of California, San Diego

Vimentin promotes collective cell migration through collagen networks via increased matrix remodeling and spheroid fluidity.
Invasion Dynamics of Multifocal Breast Tumor Spheroids in Three-dimensional Extracellular Matrix.
Perivascular Matrix Densification Dysregulates Angiogenesis and Activates Pro-Inflammatory Endothelial Cells.
Degradable multi-arm PEG hydrogels with tunable stiffness and diffusivity.
Extracellular matrix cross-talk with proteases: A master switch for remodeling and cell regulation in health and disease.
Hierarchical stabilization of bioactive hydrogels by multi-arm peptide-polymer supramolecular staples.
Basement membrane turnover drivesfilopodial protease-independent invasion.
Analyzing cell migration history in vivo using fluorescent fibrillar collagen trails.

Commun Biol. 2026 Jun 18.

Vimentin promotes collective cell migration through collagen networks via increased matrix remodeling and spheroid fluidity.

Minh Tri Ho Thanh, Arun Poudel, Shabeeb Ameen, Bobby Carroll, M Wu, Pranav Soman, Tao Zhang, J M Schwarz, Alison E Patteson.

Intermediate filaments (IF) are diverse and cell-type specific. The IF protein vimentin, expressed in mesenchymal cells and different cancer cells, is functionally associated with cell migration through fibrous tissues. Vimentin increases cell elongation needed for migration, yet also acts as a cytoskeletal cage that hinders cells squeezing through small spaces. To determine how vimentin facilitates cell migration through the extracellular matrix (ECM) and around neighboring cells in tissues, we examine the collective invasion of cell spheroids embedded in collagen networks. Unlike single-cell migration in collagen networks, the collective invasion of cells through the collagen network is increased by vimentin for both mouse embryonic fibroblasts (MEF) and co-cultures of MEF with MDA-MB-231 breast cancer cells. Using multiple experimental systems, we show that vimentin increases spheroid contractility and that vimentin-mediated collective cell expansion depends on matrix metalloproteinases (MMP), which degrade collagen networks. In addition, through advanced imaging and a computational 3D cell vertex model, we find that vimentin enhances the elongation of cells in spheroids embedded in collagen, indicating increased spheroid fluidity and active collagen contraction. Altogether, these results reveal new insights on vimentin's effects in enhancing collective cell migration in 3D matrix environments through collagen remodeling and tissue fluidity.

DOI: https://doi.org/10.1038/s42003-026-10506-3
Biophys J. 2026 Jun 16. pii: S0006-3495(26)00443-1. [Epub ahead of print]

Invasion Dynamics of Multifocal Breast Tumor Spheroids in Three-dimensional Extracellular Matrix.

Madison L Kucera, Matthew Hines, David Keeney, Austin Naylor, Yang Jiao, Bo Sun.

Breast cancer in human patients often occur as multifocal lesions and the mechanisms through which primary tumors in proximity interact with each other is not well understood. Here we study an in vitro model of bifocal breast tumors by embedding tumor spheroids of MDA-MB-231 cells in 3D extracellular matrices (ECM) made of type I collagen at different concentrations. Combining quantitative experiment, mathematical modeling and numerical simulation, we show that collective traction force from the spheroids creates dipolar deformation in the ECM. As a result in the inter-spheroid region we see increased ECM alignment and decreased pore size. The effect is particularly pronounced for soft ECM, and leads to the spatial gradient of ECM microstructure. Guided by mechanical cues, cancer cells disseminating from spheroids exhibit strong polarization, but reduced speed and persistence in the inter-spheroid space. As a result, expansion rate of bifocal spheroids decreases over time, exhibiting self-limiting dynamics. Our results suggest that reciprocal interactions between cancer cells and ECM could mechanically connect multifocal lesions, altering the invasion dynamics of breast cancer in the tissue space.

DOI: https://doi.org/10.1016/j.bpj.2026.06.017
Adv Sci (Weinh). 2026 Jun 17. e10448

Perivascular Matrix Densification Dysregulates Angiogenesis and Activates Pro-Inflammatory Endothelial Cells.

Jingyi Xia, William Y Wang, Kyle A Jacobs, Kairav Maniar, Daphne Lin, Evan H Jarman, Daniel L Matera, Kristen Loesel, Christopher D Davidson, Harrison L Hiraki, Xiaotian Tan, Eve H Shikanov, Robert N Kent, Carole Parent, Xudong Fan, Ariella Shikanov, Matthew L Kutys, Brendon M Baker.

  The potential for fibrosis across most organ systems may stem from connections to wound healing and the widespread presence of vascular endothelium. Endothelial cells (ECs) and angiogenesis have been heavily implicated in many organ-specific fibrotic conditions, but little has been established in terms of how EC phenotype governs tissue healing vs. fibrosis. Here, we examined a murine lung injury model enabling EC lineage tracing and observed the invasion of aberrant ECs from the bronchial microvasculature following injury, along with concurrent densification of surrounding extracellular matrix fibers. To investigate mechanisms governing their appearance, we established a microphysiological system of human microvessels embedded within a tunable stromal matrix and found that heightened fiber density drives endothelial to mesenchymal transition to promote aberrant tip EC (ATEC) invasion into the matrix. ATECs remained adherent to fibrotic matrix and possessed a pro-inflammatory phenotype that secretes TGF-β2. Mechanistically, we identify ATEC formation was gated by destabilization of EC adherens junctions upon adhesion to fibrous matrix and associated regulation of TGF-β signaling through a novel VE-cadherin - TGF-βR2 interaction. Altogether, this work identifies how enhanced fiber density associated with fibrogenesis regulates EC phenotype to generate pro-inflammatory ATECs and suggests new contributions of ECs to fibrotic progression.

Keywords:  TGF‐β signaling; adherens junctions; angiogenesis; bleomycin; cell migration; endothelial cells; endothelial‐mesenchymal transition; extracellular matrix; fibrosis; microphysiologic systems

DOI:  https://doi.org/10.1002/advs.202510448
Biomater Sci. 2026 Jun 17.

Degradable multi-arm PEG hydrogels with tunable stiffness and diffusivity.

Kristie Cheng, Evelyn Lim, Brett Stern, Janet Zoldan, Nicholas Peppas.

The bone marrow extracellular matrix (BM-ECM) has distinct mechanical and biochemical subniches, in which hematopoietic stem cells (HSCs) reside, self-renew, and differentiate into immune cells. Stiffness and diffusivity are key mechano-regulators of HSC fate. To control these key microenvironment parameters, we prepared a poly(ethylene-glycol) norbornene (PEGNB)-modified hydrogel platform with tunable stiffness and solute diffusivity by varying the polymer volume fraction, the number of macromolecular arms, their arm length, and their crosslinker type. The latter was identified as either nondegradable dithiothreitol (DTT) or matrix metalloproteinase (MMP)-degradable peptides. We characterized 24 PEGNB hydrogels for stiffness, swelling, and solute diffusion. Hydrogel swelling ratios ranged from 0.89 to 2.48 for DTT-crosslinked networks and 1.49 to 4.86 for peptide-crosslinked networks, supporting solvent retention for cell culture. Storage moduli ranged from 6.4 to 44.8 kPa (DTT-crosslinked networks) and 3.6 to 32.7 kPa (peptide-crosslinked networks), within the physiological range of the BM-ECM. Solute diffusivity values were also evaluated for all hydrogel formulations. Introduction of an MMP-sensitive crosslinker maintained the same relationship among hydrogel stiffness, swelling and solute diffusion while allowing for cell-mediated remodeling and high cell viability. Unlike prior predictive models, our study accounts for structural complexity to better match in vivo conditions. Therefore, we present a modular framework for engineering PEGNB hydrogels with independently tunable mechanical and transport properties, providing a robust, physiologically relevant platform to investigate stem cell-matrix interactions and advance stem cell-based tissue engineering.

DOI: https://doi.org/10.1039/d6bm00440g
FEBS J. 2026 Jun 16.

Extracellular matrix cross-talk with proteases: A master switch for remodeling and cell regulation in health and disease.

Nikos K Karamanos.

  The extracellular matrix (ECM) is a dynamic three-dimensional macromolecular network essential for maintaining tissue homeostasis. Apart from its structural and biomechanical support to tissues, the ECM plays regulatory roles in cellular signaling, cell functional properties, and morphology. The composition and structural characteristics of the ECM are widely variable among different tissues, adapting to diverse functional needs. The extensive and dysregulated remodeling of the ECM network in various diseases-such as cancer, fibrosis, and vascular and inflammatory conditions-influences their progression. ECM remodeling involves not only proteolytic degradation but also the deposition of newly synthesized matrix components that influence cellular behavior. In this special issue on ECM cross-talk with proteases, the categories and functions of various proteases are presented and discussed in terms of their involvement in ECM remodeling and cell regulatory effects. Emphasis is placed on the roles of matrix metalloproteinases (MMPs), cathepsins, a disintegrin and metalloproteinase (ADAM), a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS), components of the plasminogen activation system, and lysyl oxidase (LOX) family enzymes-both in the degradation of ECM macromolecules (collagen, elastic fibers, proteoglycans) and in their impact on extracellular vesicles (EVs) and microRNAs (miRNAs).

Keywords:  LOX, ADAM, ADAMTS; cathepsin; extracellular matrix; proteases; remodeling, matrix metalloproteinase

DOI:  https://doi.org/10.1111/febs.70626
J Mater Chem B. 2026 Jun 10.

Hierarchical stabilization of bioactive hydrogels by multi-arm peptide-polymer supramolecular staples.

Somayeh Taheri, Md Shariful Islam, Riddhesh B Doshi, Jitendra Mata, Ashley K Nguyen, Juanfang Ruan, Richard D Tilley, Kristopher A Kilian.

Supramolecular peptide hydrogels offer attractive bioactivity and dynamic mechanical behavior for three-dimensional cell culture and tissue engineering. However, their broader use is often limited by slow gelation and insufficient mechanical stability. Here, we introduce a molecular design strategy in which a tryptophan zipper pendant multiarm poly (ethylene glycol) (Trpzip-PEG) conjugate is incorporated into Trpzip nanofibrillar hydrogels to facilitate hierarchical tuning of materials properties. Trpzip peptides self-assemble into entangled nanofiber networks, while the addition of Trpzip-PEG conjugate induces reorganization of these assemblies. Electron microscopy and neutron scattering reveal more densely bundled fibers with increased microporosity and a fractal network architecture, suggesting that the conjugate acts as a supramolecular binder or "staple" coordinating nano- and micro-scale organization. These structural changes markedly accelerate gelation and increase stiffness, yield behavior, and thixotropic recovery. Importantly, the Trpzip/Trpzip-PEG supramolecular hybrid hydrogels remain cytocompatible, supporting adipose-derived stem cell adhesion, viability, and proliferation over time. Together, these findings demonstrate that Trpzip/Trpzip-PEG hybrid hydrogels offer a versatile platform for engineering mechanically robust yet bioactive soft materials for 3D cell culture, biofabrication, and regenerative medicine applications.

DOI: https://doi.org/10.1039/d6tb00490c
J R Soc Interface. 2026 Jun 17. pii: 20251106. [Epub ahead of print]23(239):

Basement membrane turnover drivesfilopodial protease-independent invasion.

David Hernandez-Aristizabal, Anotida Madzvamuse, Frédéric Luton, Rachele Allena.

  Basement membranes (BMs) are specialized, nanoporous extracellular matrices (ECMs) mainly composed of collagen IV fibres and laminins. Because collagen IV fibres form covalent cross-links (CCLs), cells cannot freely cross BMs. BM breaching marks the transition from in situ to invasive carcinoma, commonly attributed to protease activity. However, recent data show tumour cells crossing BMs through protease-independent mechanisms. Experimental evidence suggests that filopodia can play an active role in pore enlargement in extracellular matrices by generating plastic mechanical deformation. Moreover, plasticity can be regulated by CCL concentration, which we hypothesize responds to collagen IV turnover, thus generating transient weak spots. To test this, we developed a biophysical, mathematical model describing the interaction between a tumour-cell cluster (TCC) and a BM considering experimentally measured parameters of filopodial activity and collagen IV turnover taken from the literature. The cluster is represented as an evolving energetic surface, while the BM is described as a point set representing active and inactive links. Simulations show that synchronization of collagen IV turnover, coupled with filopodium extension, drives pore enlargement, providing a mechanistic basis for protease-independent invasion. Consistent with experimental observations, simulations identify two complementary filopodium groups: one driving global degradation and another promoting local pore enlargement.

Keywords:  basement membrane; cancer invasion; collagen IV covalent cross-link; collagen IV turnover; evolving surface finite-element method; filopodia; geometric-surface PDE modelling

DOI:  https://doi.org/10.1098/rsif.2025.1106
Commun Biol. 2026 Jun 19.

Analyzing cell migration history in vivo using fluorescent fibrillar collagen trails.

Zhongming Chen, Branden S Moriarity, Paolo P Provenzano.

Cell migration is a critical process in development, homeostasis, and disease. While cell migration in vitro is well investigated, much less is known about migration deep within tissues, largely due to limitations associated with deep cell imaging in tissues. In this study, we investigated cell migration history in vivo by developing a strategy based on recording cell trails formed by fusion of fluorescent protein and collagen secreted by migrating cells. By engineering different cell lines to express either fluorescent protein-fused Col1a1 or Col1a2 we identified trails formed in normal mouse tissues as well as primary tumors and metastatic organ sites. Analyses of the trail patterns revealed the paths taken by migrating cells and regions that suggest group trails, including trails along vascular adventitia. These results demonstrate that cell migration history can be traced in mouse models through postmortem analysis of normal and cancerous tissues.

DOI: https://doi.org/10.1038/s42003-026-10488-2