bims-ecemfi Biomed News
on ECM and fibroblasts
Issue of 2026–06–14
eight papers selected by
Badri Narayanan Narasimhan, University of California, San Diego



  1. Adv Healthc Mater. 2026 Jun 06. e03969
      Particle-based hydrogels have been used as injectable scaffolds, biomaterial inks for extrusion bioprinting, and permissive systems for 3D cell culture owing to their unique physical properties, including bulk yielding and porosity. These properties are in part governed by interparticle interactions and spatial organization, with limited potential to design these properties in systems based on spherical hydrogel microparticles. Here, we engineer particle-based hydrogels where each particle is a discrete electrospun hydrogel microfiber that has been segmented to a length of 93 ± 51 µm, with a diameter of 1.6 ± 0.3 µm, presenting unique viscoelastic properties allowing stability without interparticle crosslinking (annealing). The fibers' flexibility and high aspect ratios enable interactions among fibers that give packed hydrogel microfiber (PHM) materials that are mechanically robust, can stretch without breaking when strained, and exhibit tissue-mimetic stress relaxation under constant strain. As cell culture scaffolds, shear-induced alignment of the individual fibers within 3D printed PHM filaments provide topographical cues to cells that promote alignment. Cells embedded in 3D within PHMs spread due to the permissive microenvironment presented by the microfibers. This work highlights strengths of fiber-based particle systems as dynamic and permissive scaffolds and printable biomaterials for tissue engineering and regenerative medicine.
    Keywords:  bioprinting; granular hydrogels; hydrogels; microfibers; viscoelasticity
    DOI:  https://doi.org/10.1002/adhm.202503969
  2. Cell Oncol (Dordr). 2026 Jun 12. pii: 87. [Epub ahead of print]49(3):
       PURPOSE: The remodeling of the extracellular matrix (ECM) is a key feature of tumor development in the liver, particularly in hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA). Fibrosis and cirrhosis are risk factors for tumorigenesis and define serious structural changes in the ECM. Fibrotic-induced collagen and fibronectin alter the stiffness and heterogeneity of the ECM. A stiffened and heterogeneous ECM promotes the proliferation, migration, and invasion of tumor cells. Direct effects of structural changes in the ECM on HCC/iCCA cancer cells are insufficiently studied.
    METHODS: HCC and iCCA cells were examined in contact with differently structured collagen and collagen-fibronectin networks. The structural architecture of the networks was defined by combining the normalized stiffness, pore size, and network distribution values as the ECM Architectural Index (EAI). The effects of cell-matrix interactions on cell stiffness, invasiveness, and the ability to interact with network structures through fiber displacement in relation to network architecture were determined.
    RESULTS: Increased EAI caused a decrease in cell stiffness, an increase in cell invasiveness, and altered fiber displacements. Different effects on HCC and iCCA cells depending on the EAI were identified. High EAI resulted in low cell stiffness and high cell invasion across cancer cell types.
    CONCLUSIONS: We present a model system that is applicable to identify structurally induced influences of the extracellular matrix on cancer cells and to investigate the risk factor of structural changes in the tumor environment.
    Keywords:  Extracellular matrix; Fibrosis; Hepatocellular carcinoma; Intrahepatic cholangiocarcinoma
    DOI:  https://doi.org/10.1007/s13402-026-01235-0
  3. Cell Rep. 2026 Jun 09. pii: S2211-1247(26)00601-7. [Epub ahead of print]45(6): 117523
      The metastatic dissemination of individual cells or cell collectives is a decisive step in the progression of cancers. Migrating single cells dynamically switch between mesenchymal traction-based and amoeboid propulsion-based modes of migration in a mechanism named plasticity. Collective cell migration has mainly been described as a traction-dependent mode of locomotion. While a propulsive collective cell migration has recently been reported, we question whether cell clusters are also endowed with plasticity. Here, we report that patient-derived digestive cancer organoids exhibit a preferred mode of migration but transition to the alternate strategy to adapt to external stimuli or to the manipulation of intrinsic determinants. We show that the tumor cell cluster plasticity observed in vitro ensures efficient metastatic seeding in a murine model of peritoneal carcinomatosis. These findings reveal an adaptive mechanism at play during tumor invasion that must further be decrypted to enable the design of therapeutic strategies halting metastatic progression.
    Keywords:  CP: cancer; CP: cell biology; actomyosin contractility; collective cell migration; colorectal and pancreatic tumor organoids; mouse peritoneal carcinomatosis model; plasticity; β1-integrin
    DOI:  https://doi.org/10.1016/j.celrep.2026.117523
  4. iScience. 2026 Jun 19. 29(6): 116191
      Traditional single-network hydrogels are limited by trade-offs among key mechanical properties, such as elastic modulus and toughness, and are further compromised by structural defects introduced during synthesis. These constraints significantly hinder their performance in demanding applications. Here, we propose a network-refinement strategy using repeated crosslinking to achieve comprehensive mechanical reinforcement. Through network refinement, structural defects within polymer networks are progressively filled, and both the network homogeneity and effective chain density are improved. The reinforced hydrogels exhibit up to a 6-fold increase in elastic modulus, a 10-fold enhancement in fracture toughness, a 20-fold increase in tensile strength, and a 42-fold improvement in work of fracture, while maintaining high stretchability and negligible hysteresis under moderate deformation. This universal strategy provides an effective route to comprehensively enhance the mechanical properties of hydrogel-like materials, paving the way for robust soft materials in applications such as cardiac healing patches, load-bearing biomedical implants, and wearable electronics.
    Keywords:  Materials science; Mechanical property; Polymers
    DOI:  https://doi.org/10.1016/j.isci.2026.116191
  5. Proc Natl Acad Sci U S A. 2026 Jun 16. 123(24): e2524496123
      Cell migration across epithelial barriers occurs in diverse developmental, immunological, and pathological contexts. Here, we investigate the contribution of heterotypic adhesion between migrating cells and epithelial "substrate" cells to transepithelial migration. Using an in silico model inspired by the migration of primordial germ cells across the midgut epithelium in the Drosophila embryo, we show that heterotypic adhesion modulates migration efficiency in a nonmonotonic manner, revealing the existence of an optimal adhesion regime. Consistent with this prediction, in vivo overexpression of E-cadherin in germ cells accelerated their exit from the midgut relative to controls. Beyond providing experimentally testable predictions, our model integrates and explains previous observations on the role of heterotypic adhesion in cell-on-cell migration, offering a framework for understanding transepithelial migration across biological contexts.
    Keywords:  Cellular Potts model; CompuCell3D; E-cadherin; germ cell migration; intercellular adhesion
    DOI:  https://doi.org/10.1073/pnas.2524496123
  6. ACS Biomater Sci Eng. 2026 Jun 12.
      Protein-based hydrogels synthesized from covalently cross- linked globular proteins are an emerging class of biomaterials, yet their dense nanoscale network architecture severely limits permeability to large biomolecules. Here, we report a general strategy to create highly permeable polyprotein hydrogels by photochemically cross-linking engineered octameric repeats of antibody-binding Protein A or Protein L in the presence of a transient alginate network, which can function as high-capacity affinity matrices. We demonstrate that the coordination capacity per domain controls the cross-linked shell that forms around growing pores during competitive gelation, with higher coordination (Protein L) producing a denser shell and more numerous but smaller pores and lower coordination (Protein A) yielding larger pores. The resulting hydrogels enable rapid and deep penetration of antibodies throughout the entire material volume while retaining high functional-domain density. When used as model affinity matrices, these materials display exceptional binding capacity, near-quantitative recovery, and excellent operational and shelf stability. This work establishes a molecular design rule for tuning porosity in folded-protein biomaterials and opens a route to next-generation, fully protein-based scaffolds with programmable permeability and function.
    Keywords:  affinity biomaterials; antibody purification columns; coordination-controlled porosity; photochemical cross-linking; protein-based hydrogels; transient double-network
    DOI:  https://doi.org/10.1021/acsbiomaterials.6c00634
  7. bioRxiv. 2026 Jun 06. pii: 2026.06.02.729677. [Epub ahead of print]
      We experimentally assess the nonlinear rheology of composite biopolymer hydrogels composed of thiolated hyaluronic acid, poly(ethylene glycol) diacrylate (PEGDA), and laminin-111 in varied concentrations. We focus in particular on the influence of laminin on the mechanics of the assembled hydrogels, reporting nonlinear rheological measurements for gels under applied shear and compressive load. We find that increasing the concentration of laminin in the synthesized gels reduces the linear shear modulus and gives rise to a mild strain softening regime at intermediate strains prior to the onset of strain stiffening. In the stiffening regime, we find that all gels exhibit stress-controlled mechanics with K ∝ σ a , with an apparent stiffening exponent of a ≈ 1, in agreement with observations of a variety of other reconstituted biopolymer gels. We discuss the possible implications of this nonlinear mechanical behavior on mechanotransduction and organoid development in biomimetic extracellular matrices.
    DOI:  https://doi.org/10.64898/2026.06.02.729677
  8. J Cell Sci. 2026 Jun 10. pii: jcs.264323. [Epub ahead of print]
      Epithelial cells primarily segregate transmembrane proteins to apical or basal surfaces, establishing apical-basal polarity. For 3D tissues, apical proteins face inwards. Recent work by our group showed that increased RhoA activation causes epithelial spheroids to invert apical-basal polarity via a collective rearrangement of cells, a process we and others have termed eversion. In this work we determined that α6ß4-laminin interactions are required for spheroids to evert to apical-out polarity. Additionally, we show that increased cell proliferation and anchorage independence are required to sustain apical-out polarity. We also observed that apical-out spheroids can 'revert' to apical-in polarity through apoptotic cavitation of cells located in the center of the spheroids. This study provides new mechanistic insights into the biochemical and biophysical mechanisms that drive eversion and maintain apical-out polarity, and supports the concept that apical-basal polarity orientation may drive phenotypic switching of epithelia.
    Keywords:  Anchorage-independence; Apical-basal polarity; Integrins
    DOI:  https://doi.org/10.1242/jcs.264323