bims-ecemfi Biomed News
on ECM and fibroblasts
Issue of 2025–12–07
seven papers selected by
Badri Narayanan Narasimhan, University of California, San Diego
  1. Rotational migration in human pancreatic ductal organoids depends on actin and myosin activity.
  2. Scale-Specific Viscoelastic Characterization of Hydrogels: Integrated AFM and Finite Element Modeling.
  3. Highly Tunable and Cell-Remodelable Thiol-ene Alginate-Peptide Crosslinked Hydrogels to Recreate Cellular and Organoid Microenvironments for Biofabrication.
  4. Biomechanical Phenotyping Reveals Unique Mechanobiological Signatures of Early-Onset Colorectal Cancer.
  5. Surface tension-driven persistence: How hydrogel interfacial properties regulate fibroblast directional migration.
  6. Compression-Tension-Asymmetry and Stiffness Nonlinearity of Collagen-Matrigel Composite Hydrogels.
  7. Controlling Polymerization-Induced Phase Separation in the Synthesis of Porous Gels.
  1. Commun Biol. 2025 Dec 05. 8(1): 1749
    Rotational migration in human pancreatic ductal organoids depends on actin and myosin activity.
    Gengqiang Xie, Chaity Modak, Olalekan H Usman, Raphael W F Tan, Nicole Coca, Gabriela De Jesus, Yue Julia Wang, D Thirumalai, Xin Li, Jerome Irianto.
      Rotational migration is one specific form of collective cell migration when epithelial cells are confined in a spherical geometry, such as in the epithelial acini. This tissue-level rotation motion is crucial for the morphogenesis of multiple epithelial systems. Here, we introduce human pancreatic ductal organoids as a model to study rotational migration. Live imaging revealed the persistent rotation of the organoids over time. By tracking the nuclei, the three-dimensional trajectory of the cellular movement was reconstructed and the velocity of the rotation was quantified. The presence of focal adhesion clusters and prominent actin stress fibers were observed at the basal side of the organoids, suggesting the interactions between the cells and the surrounding extracellular matrix. Finally, our inhibition study showed the dependence of pancreatic ductal organoid rotational migration on myosin activity, actin polymerization, and actin branching. We hope that this model will enable future studies with human primary cells, which are more faithful to normal epithelial cells.
    DOI:  https://doi.org/10.1038/s42003-025-09136-y
  2. Small. 2025 Dec 03. e07835
    Scale-Specific Viscoelastic Characterization of Hydrogels: Integrated AFM and Finite Element Modeling.
    Nicole Fertala, Klemens Uhlmann, Evgeny Grigoryev, Prannoy Seth, Jens Friedrichs, Julian Thiele, Carsten Werner, Daniel Balzani.
      Viscoelastic hydrogels mimic the dynamic mechanical properties of native extracellular matrices, making them essential for biomedical applications. However, characterizing their scale-dependent mechanical properties remains challenging, despite their critical influence on cell-material interactions and biomaterial performance. Here, an integrated experimental-computational approach is presented to quantify and model the viscoelastic behavior of interpenetrating polymer network hydrogels across micro- and macro-scales. Atomic force microscopy-based stress relaxation tests revealed that microgels exhibit rapid, localized relaxation, while macroscopic bulk gels displayed prolonged relaxation dominated by poroelastic effects. Finite element simulations accurately replicated experimental conditions, enabling the extraction of key parameters: fully relaxed elastic modulus, relaxation modulus, and relaxation time constant. A novel analytical model is further developed to predict viscoelastic parameters from experimental data with minimal error (<6%), significantly streamlining characterization. The findings highlight the necessity of scale-specific mechanical analysis and provide a robust platform for designing biomaterials with tailored viscoelasticity for tissue engineering and regenerative medicine.
    Keywords:  atomic force microscopy; finite element modeling; interpenetrating polymer networks; scale‐dependent mechanics; viscoelastic hydrogels
    DOI:  https://doi.org/10.1002/smll.202507835
  3. Adv Healthc Mater. 2025 Dec 03. e04313
    Highly Tunable and Cell-Remodelable Thiol-ene Alginate-Peptide Crosslinked Hydrogels to Recreate Cellular and Organoid Microenvironments for Biofabrication.
    Julia Fernández-Pérez, Adrián Seijas-Gamardo, Antonio J Feliciano, Panagiota Kakni, Anna M Kip, Paul Wieringa, Stefan Giselbrecht, Matthew B Baker, Lorenzo Moroni.
      In this study, a cell-mediated degradable alginate hydrogel system for organoid culture and amenable to biofabrication technologies is presented. Norbornene-functionalized alginate is crosslinked with a di-thiolated peptide sequence cleavable by matrix metalloproteinases and decorated with cysteine-terminated cell-adhesion peptide RGD, upon exposure to UV. Stiffness of the hydrogels can be controlled by tuning polymer and crosslinker concentrations. Pre-gel solutions are successfully bioprinted with a pneumatic extrusion-based system. The hydrogels are used to encapsulate a variety of sensitive cell types. Human endometrial organoids present high cell viability, grow in size over time, present spherical morphology, and express cell-cell contacts E-cadherin and proliferation marker Ki67. Encapsulated mouse embryonic stem cell-derived thyroid follicles produce thyroglobulin and T4. Mouse intestinal organoids adopt a proliferative phenotype. Vascularization inside the hydrogels is achieved using endothelial cells and supporting cells (single cell suspension and spheroids). Neurite outgrowth, both small and thick bundles, from encapsulated iPSC-derived neurospheres, demonstrates the reinnervation potential of the hydrogel. This polysaccharide hydrogel platform could be used as a defined, tunable, and ethical alternative to mouse sarcoma-extracted basement-membrane matrices.
    Keywords:  alginate; cellular microenvironment; hydrogels; organoids; thiol‐ene chemistry
    DOI:  https://doi.org/10.1002/adhm.202504313
  4. Adv Sci (Weinh). 2025 Dec 01. e14693
    Biomechanical Phenotyping Reveals Unique Mechanobiological Signatures of Early-Onset Colorectal Cancer.
    Nicole C Huning, Munir H Buhaya, Victor V Nguyen, Afeefah Khazi-Syed, Haider A Ali, Adil Khan, Angela Fan, Robert C Fisher, Zhikai Chi, Indu Raman, Guangchun Chen, Chengsong Zhu, Mengxi Yu, Andrew R Jamieson, Sara Roccabianca, Victor D Varner, Cheryl M Lewis, Emina H Huang, Jacopo Ferruzzi.
      While both incidence and mortality of sporadic average-onset colorectal cancer (AO CRC, above 50 years of age) are in constant decline, sporadic early-onset colorectal cancer (EO CRC, under 50 years of age) is rising rapidly. Yet, the causes behind this rise remain poorly understood. Epidemiological studies indicate that lifestyle and environmental exposures may result in chronic inflammation, which is known to trigger tissue fibrosis. This study tests the hypothesis that fibrotic remodeling and biomechanical stiffening of colorectal tissues represent measurable hallmarks and potential drivers of EO CRC. Using primary human tissues, this work shows that EO CRC is associated with changes in collagen microstructure, increased stiffness, and elevated viscosity of primary tumors. Spatial transcriptional profiling and immunostaining reveal pro-fibrotic signatures in stromal cells, alongside enhanced Yes-associated protein (YAP) mechanotransduction and proliferation in epithelial cells of EO CRC tissues. Mechanistically, increasing matrix stiffness in vitro promotes proliferation of epithelial cells in 2D and 3D colorectal cancer models. Together, these findings establish EO CRC as a disease marked by early and widespread biomechanical remodeling, suggesting that a fibrotic and stiffened tissue microenvironment may orchestrate EO CRC tumor initiation.
    Keywords:  YAP mechanotransduction; average‐onset; biomechanics; colorectal cancer; early‐onset; fibrosis; stiffness
    DOI:  https://doi.org/10.1002/advs.202514693
  5. Acta Biomater. 2025 Nov 27. pii: S1742-7061(25)00894-3. [Epub ahead of print]
    Surface tension-driven persistence: How hydrogel interfacial properties regulate fibroblast directional migration.
    Sara Faour, Cyrille Vézy, Régis Déturche, Stéphane Dedieu, Jérome Sohier, Rodolphe Jaffiol.
      The development of viscoelastic biomaterials with tunable mechanical properties is a key issue in a wide range of applications in mechanobiology. While numerous foregoing works have revealed the impact of bulk matrix stiffness on cellular and multicellular responses, few have examined the effect of interfacial mechanical properties, such as surface tension σ. Owing to the elastocapillarity phenomenon, σ of soft materials can dominate their bulk mechanical properties and thus regulate cellular response. To address this complex issue of mechanotransduction largely overlooked in the literature, this study introduces a new polymer-based hydrogel that provides fine control of σ. This hydrogel is composed of short polyethylene glycol (PEG) elastic units, cross-linked with poly-L-lysine dendrigrafts (DGL). The stiffness and interfacial mechanical properties of this hydrogel are controlled by adjusting the DGL/PEG ratio and mechanically characterized with optical tweezers. This powerful optical technique enables active microrheology and surface micro-indentation to assess, with the same setup, elastic modulus and surface tension. To demonstrate the key impact of σ in mechanotransduction, 2D fibroblast migration experiments are conducted on fibronectin-coated hydrogels. Single-cell trajectories were tracked using epi-fluorescence imaging, and direction and speed autocorrelations were computed and analysed using the "stick-slip" model. This study highlights, for the first time, that cells can adopt directional persistence migration when surface tension increases. Statement of Significance: A hydrogel composed of PEG and poly-L-lysine dendrigraft has been developed to tune the surface tension of soft materials designed to mimic biological tissues. This interfacial mechanical property was successfully characterized using optical tweezers, after which the two-dimension directional persistent motion of fibroblasts was studied according to the surface tension of hydrogel.
    Keywords:  Cell adhesion and motility; Elastocapillarity; Hydrogel; Optical tweezers; Persistent migration; Soft matter rheology
    DOI:  https://doi.org/10.1016/j.actbio.2025.11.058
  6. Adv Healthc Mater. 2025 Dec 05. e03052
    Compression-Tension-Asymmetry and Stiffness Nonlinearity of Collagen-Matrigel Composite Hydrogels.
    David Böhringer, Jan Hinrichsen, Radik Gataulin, Sandra Wiedenmann, Marina Spörrer, Selda Sherifova, Paul Steinmann, Gerhard A Holzapfel, Ben Fabry, Silvia Budday.
      Collagen type I hydrogels, which self-assemble into 3D fiber networks, are commonly used for cell culture and tissue engineering applications. Collagen hydrogels replicate the nonlinear stress-strain relationship of collagenous tissue under extension. However, they buckle and soften under compression, whereas natural tissue exhibits significant stiffening due to the presence of cells and other matrix components. To more closely mimic the mechanical properties of natural tissue, varying concentrations of the basement membrane extract Matrigel are added to collagen. The stress-strain relationship of the resulting composite hydrogels is then analyzed under compression, tension, and shear. It is found that the addition of Matrigel increases the stiffness and reduces the compression-tension asymmetry. This can be explained by a reduced degree of freedom for collagen fiber buckling due to the constraints imposed by the surrounding fine-meshed Matrigel network. Consistent with this explanation, it is found that the collapse of composite hydrogels under uniaxial strain decreases with increasing concentration of Matrigel and other filler materials, such as alginate. Taken together, by adjusting the ratio of Matrigel to collagen, the mechanical compression-tension asymmetry and nonlinearity of composite hydrogels can be tuned to more closely mimic natural tissue and tailor cell behavior.
    Keywords:  biopolymer; finite element method; mechanical testing; ogden model; parameter identification
    DOI:  https://doi.org/10.1002/adhm.202503052
  7. ACS Nano. 2025 Dec 02.
    Controlling Polymerization-Induced Phase Separation in the Synthesis of Porous Gels.
    Yanxia Feng, Noel Ringeisen, Eric R Dufresne, Lucio Isa, Robert W Style.
      Porous gels, gels with solvent-filled pores that are much larger than their mesh size, are widely used in engineering and biomedical applications due to their tunable mechanics, high water content, and selective permeability. Among various strategies to create porous gels, polymerization-induced phase separation (PIPS) has shown particular promise. However, the conditions that trigger and control PIPS are poorly understood. Here, we systematically investigate the influence of solvent quality, polymeric precursor molecular weight, and polymer concentration on phase separation in polymerizing poly(ethylene glycol) diacrylate gels. Phase separation occurs when the precursor solution concentration is below the overlap concentration. Phase-separated gels have a pore geometry that is controlled by solvent quality: better solvents result in smaller pores, while worse solvents can create superporous, highly absorbant gels. Motivated by our results, we propose a theory that predicts when phase separation occurs in polymerizing gels, applicable across a wide range of polymer/solvent gel systems. Our results provide a framework for the rational design of porous gels.
    Keywords:  PEGDA; overlap concentration; phase separation; polymer gel; porosity; superporous gel
    DOI:  https://doi.org/10.1021/acsnano.5c14313
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