bims-ecemfi 2026-10-11 papers

Biomater Adv. 2026 Sep 21. pii: S2772-9508(26)00492-9. [Epub ahead of print]191 215192

Effect of hydrogel properties on fibroblast morphodynamics.

Fatemeh Rasti Boroojeni, Nina Reustle, Viktoria Schoen, Sajjad Naeimipour, Johan Junker, Pierfrancesco Pagella, Daniel Aili.

Cellular morphodynamics are tightly regulated by the mechanical and biochemical properties of the extracellular matrix (ECM), yet independently investigating these cues in 3D hydrogel models remains challenging. Here, we present a modular hyaluronic acid (HA)-based hydrogel system that enables systematic modulation of stiffness, degradability, and viscoelasticity to examine the regulation of fibroblast behavior. Using strain-promoted azide-alkyne cycloaddition (SPAAC) chemistry, we engineered nanoporous HA hydrogels of defined stiffness while maintaining constant polymer density and ligand presentation. Fibroblast morphology showed a non-monotonic dependence on hydrogel formulation, with the most pronounced spreading observed in the ∼400 Pa formulation. Cells in softer and stiffer hydrogels remained mostly rounded. Protease-degradable crosslinkers accelerated, but were not strictly required for, morphological transitions, and comparison with alginate hydrogels of similar stiffness suggested a role for HA-specific remodeling mechanisms. Incorporation of xanthan gum introduced viscoelastic and viscoplastic behavior into the predominantly elastic HA hydrogels, which supported pronounced fibroblast spreading. These findings demonstrate that fibroblast morphodynamics in 3D are governed by an interplay between stiffness, enzymatic degradability, matrix identity, and time-dependent mechanical behavior. The presented hydrogel system provides a versatile platform for interrogating cell-matrix interactions and for engineering instructive microenvironments in tissue models and regenerative medicine.

Keywords: 3D cell culture; Cell-matrix interactions; Degradable hydrogels; Fibroblasts; Hydrogels; Mechanobiology; Viscoelasticity

DOI: https://doi.org/10.1016/j.bioadv.2026.215192

Nat Commun. 2026 Sep 08. pii: 10622. [Epub ahead of print]17(1):

Contact percolation governs collective motility via mechano-chemical feedback in heterogeneous breast cancer.

Breast carcinomas are heterogeneous tissues containing cell populations with distinct molecular programs and mechanical states. How this heterogeneity drives collective invasion remains unclear. Tissue fluidization, the shift from a crowded, solid-like state to a more deformable and mobile one, promotes collective motion of cancer cells. Using percolation theory, which explains how connected clusters generate system-wide behavior, here we show that a critical fraction of motile cells expressing RAB5A, a membrane-trafficking regulator, triggers an abrupt transition to coordinated, flock-like movement in heterogeneous breast cancer monolayers. Above this threshold, RAB5A cells form connected networks that mechanically and chemically reprogram neighboring control cells. Under these conditions, control cells acquire aligned migratory protrusions, soften and elongate through E-cadherin-dependent EGFR-MAPK signaling. They further activate a STAT1/STAT2-dependent inflammatory gene program through both cell contact and soluble signals. Our findings reveal a mechano-chemical switch through which local tumor heterogeneity organizes tissue-wide fluidization, inflammation and invasive behavior in breast cancer.

DOI: https://doi.org/10.1038/s41467-026-77357-8

Bioact Mater. 2027 Mar;69 18-32

Matrix nanoalignment programs macrophage vesicular immunity through TRPV2 mechanogating.

Bohan Yin, Guangli Xiang, Ziqi Zhang, Limeng Zheng, Runyao Wang, Qin Zhang, Yingying Huang, Chenjie Liu, Jingjing Chi, Xinyue Xia, Jiaxiang Yan, Jianfang Wang, Mo Yang, Liming Bian, Siu Hong Dexter Wong.

The extracellular matrix (ECM) undergoes extensive architectural remodeling during tumor progression, generating nanoscale alignment cues that profoundly influence behaviors of immune cells. However, whether ECM nanoarchitecture directly programs their immune secretory functions remains poorly defined. Here, we develop a magnetically switchable hydrogel that enables reversible, on-demand modulation of nanoscale ligand alignment without altering bulk stiffness or composition. Using this platform, we uncover a mechanotransduction pathway in tumor-associated macrophages (TAMs) whereby matrix nanoalignment enhances integrin β1-dependent mechanosensing and transient receptor potential cation channel subfamily V member 2 (TRPV2)-dependent Ca2+ signaling, thereby promoting phosphoinositide 3-kinase (PI3K)-Ras-related protein 11a (Rab11a)-associated small extracellular vesicle (sEV) release by approximately tenfold. Beyond increasing vesicle output, PI3K-mechanistic target of rapamycin complex 2-associated signaling altered the particle-normalized cargo profile of sEVs, with preferential enrichment of immunoregulatory molecules, including M2-promoting cytokines and miR-181a-5p. These sEVs reprogram macrophages toward an immunosuppressive M2-like phenotype, suppress cytotoxic CD8+ T-cell infiltration, and accelerate melanoma progression in vivo. Importantly, selective disruption of the TRPV2-Rab11a axis or pharmacological attenuation of ECM remodeling restores antitumor immunity and restricts tumor growth. Together, our findings demonstrate that ECM nanoarchitecture is sufficient to regulate macrophage sEV programming in a defined matrix environment and identify TRPV2-associated mechanotransduction as a potential therapeutic vulnerability in matrix-remodeled tumors.

Keywords: ECM nanoarchitecture; Magnetic control; Mechanobiology; Small extracellular vesicle release; Tumor-associated macrophages

DOI: https://doi.org/10.1016/j.bioactmat.2026.09.011

J Biomed Mater Res A. 2026 Oct;114(10): e70153

The Porosity and Stiffness of Articular Cartilage Extracellular Matrix Derived Scaffolds Modulate Chondrogenesis of Mesenchymal Stromal Cells.

Giovanni Gonnella, Tosca Roncada, Daniel J Kelly.

Articular cartilage (AC) regeneration remains a major challenge in musculoskeletal tissue engineering. Cartilage extracellular matrix (ECM)-derived scaffolds have shown promise as tissue-specific biomaterials, but the extent to which the fabrication process can be tuned to modulate scaffold pore architecture and mechanics and how this might influence the chondrogenic differentiation of mesenchymal stromal/stem cells (MSCs) remains incompletely defined. The aim of this study was to develop solubilized porcine AC-ECM scaffolds with controlled differences in pore size and matrix stiffness, and to evaluate how these factors regulate chondrogenesis of MSCs. Scaffolds with different pore sizes were fabricated by modifying the freezing cycle during lyophilization through the inclusion of an annealing step, while scaffold stiffness was varied by adjusting the AC-ECM concentration from 10 (1% ECM) to 50 mg/mL (5% ECM). Incorporation of an annealing step led to a ~2.5-fold increase in the mean scaffold pore size and was associated with improved construct elasticity and greater early cellular penetration. Increasing the AC-ECM concentration increased scaffold stiffness, with the ramp modulus increasing from approximately 5 kPa in the 1% scaffolds to approximately 60 kPa in the 5% scaffolds. All scaffold groups supported cartilage-matrix deposition during chondrogenic culture. Higher ECM concentrations were associated with greater total collagen accumulation, while the stiffest 5% scaffolds supported increased Type X collagen staining relative to the softer scaffolds. The expression of key chondrogenic genes SOX9, ACAN, and COL2A1 was higher in the 2% scaffolds compared to 5% scaffolds, while the expression of the hypertrophic marker COL10A1 was higher in the 5% scaffolds. In summary, scaffold processing provided a practical means to tune pore architecture and bulk mechanical behavior in solubilized AC-ECM scaffolds, and these differences were associated with changes in cell distribution and phenotype. These findings can potentially be leveraged to engineer scaffolds supportive of zonal cartilage tissue engineering or for osteochondral defect repair.

Keywords: articular cartilage; chondrogenesis; decellularized tissue; extracellular matrix; freeze‐drying; mechanical properties; mesenchymal stromal cells

DOI: https://doi.org/10.1002/jbm.a.70153

Proc Natl Acad Sci U S A. 2026 Oct 13. 123(41): e2608188123

Formation of a swelling gel underlies a morphological transition in Bacillus subtilis biofilms.

Ayantika Saha, Joshua M Jones, Abigail Plummer, Joseph W Larkin.

Microbes across diverse species and environments form biofilms, living materials composed of cells and extracellular polymers. Biofilm-dwelling cells benefit from emergent soft matter physics, which sculpts three-dimensional morphologies and facilitates osmotic nutrient uptake. Although biofilms are modeled as viscoelastic gels, the physical origins of the phase transition underlying their conversion from groups of cells to living gels have not been systematically investigated. Here, we show that Bacillus subtilis biofilms use polymer composition to tune their physical properties and drive gel formation. Using imaging, water immersion experiments, and rheological measurements with matrix knockout strains, we demonstrate the complementary roles of two polymers in this developmental transition: hydrophilic poly-γ-glutamic acid swells colonies by absorbing water while exopolysaccharides serve as effective cross-linkers, causing a sol-gel-like phase transition that imparts structural integrity. With matrix knockout coculture biofilms, we independently modulate the production of each polymer and reveal a phase space of biofilm morphologies. Colonies that produce both polymers develop macroscopic wrinkles. A thin-film model predicts biofilm wrinkling from swelling-induced internal strain coupled with elasticity. The model reproduces the shape of our observed morphological phase diagram. Our results demonstrate that bacteria leverage gelation to vary their material properties and morphologies, with implications for microbial ecology and engineering living matter.

Keywords: gelation; hydrogel swelling; living material; microbial communities; phase transition

DOI: https://doi.org/10.1073/pnas.2608188123