bims-ecemfi 2026-09-20 papers

bims-ecemfi

Biomed News

on ECM and fibroblasts

Issue of 2026–09–20
ten papers selected by
Badri Narayanan Narasimhan, University of California, San Diego

Adipose-mimetic granular hydrogels uncover biophysical cues driving breast cancer invasion.
Matrix degradation promotes fibronectin deposition and spatial remodeling in 3D.
Beyond stiffness: interfacial slippage and active cellular matrix remodelling in focal adhesion dynamics.
Viscotaxis: An Emerging Driver for Directed Cell Migration.
CFM: confinement force microscopy-a dynamic, precise and stable microconfiner for traction force microscopy in spatial confinement.
Crosslinker identity and dynamics regulate F-actin network structure and mechanics.
Mechanically Active Biomaterials for Stem Cell Differentiation.
Synthetic PEG-4MAL Hydrogels Support Patient-Derived Human Intestinal Enteroid Culture.
Fibronectin's tensional state as a mechanical signature of fibrotic extracellular matrix in idiopathic pulmonary fibrosis models.
Intrinsically Strain-Stiffening, Conductive, ROS-Scavenging Peptide-Polymer Hydrogel to Promote Neurite Outgrowth.

Cell Biomater. 2026 Aug 18. pii: 100411. [Epub ahead of print]2(8):

Adipose-mimetic granular hydrogels uncover biophysical cues driving breast cancer invasion.

Brianna K Knode, Garrett F Beeghly, Brittany E Schutrum, Dong Wang, Yitong Zheng, Alice Battistella, Ruchi Goswami, Chi-Yong Eom, Irina Kopyeva, Aline Bozec, Jochen Guck, Nozomi Nishimura, Salvatore Girardo, Corey S O'Hern, Claudia Fischbach.

  Breast cancer cells invade collagen type I-rich mammary adipose tissue during initial stages of metastasis, but how adipocyte mechanics regulate this process remains unclear. To elucidate these connections, we quantified the size and stiffness of primary adipocytes and replicated these properties using tunable polyacrylamide (PAAm) beads. Subsequently, we embedded these beads into type I collagen to form 3D granular hydrogels mimicking native adipose tissue architecture. Bead-embedded hydrogels demonstrated increased breast cancer cell invasion and collagen fiber organization relative to beadless controls, and cells invaded more readily in systems with decreased bead stiffness. Similarly, Discrete Element Method simulations revealed that soft beads promoted invasion by deforming in response to confined cancer cell migration. These trends were validated in vivo via intravital imaging of murine mammary tumors. Collectively, our data suggest that adipocyte mechanics regulate breast cancer invasion by coordinating both matrix architecture and cellular confinement.

Keywords:  ECM architecture; TME mechanics; adipose modeling; breast cancer; granular hydrogel

DOI:  https://doi.org/10.1016/j.celbio.2026.100411
Cell Rep Phys Sci. 2026 Aug 19. 7(8): 103489

Matrix degradation promotes fibronectin deposition and spatial remodeling in 3D.

Rabeya Sharmin Lima, Caleb Morrill, Haley A Royce, Claire Komar, Yang Hu, Linqing Li.

The extracellular matrix (ECM) coordinates the interplay between biochemical and biophysical cues to regulate cell behavior, yet isolating their individual contributions remains difficult as they are interdependent in native tissues. Here, we present a modular hydrogel platform that independently controls growth factor delivery and user-defined enzymatic matrix degradation. We show that matrix degradation alone, in the absence of exogenous growth factors, is sufficient to drive cell spreading, migration, and fibronectin deposition and assembly. Growth factor stimulation enhanced spheroid expansion but did not induce organized fibronectin remodeling unless combined with matrix degradation. Mechanistic inhibitor studies revealed that degradation-enabled fibronectin remodeling is primarily contractility dependent and MMP independent. These results support a feedback model wherein matrix degradation creates a permissive microenvironment for cell migration and fibronectin deposition, reinforcing focal adhesion formation, cell contractility, and further ECM assembly. This work identifies matrix degradation as an instructive regulator of fibronectin deposition, assembly, and remodeling, offering a framework for designing dynamic hydrogels that emulate tissue remodeling during development and healing.

DOI: https://doi.org/10.1016/j.xcrp.2026.103489
Eur Biophys J. 2026 Sep 15.

Beyond stiffness: interfacial slippage and active cellular matrix remodelling in focal adhesion dynamics.

Ivana Pajic-Lijakovic, Milan Milivojevic, Boris Martinac, Massimo Vassalli, Peter V E McClintock.

  Focal adhesion (FA) dynamics and cell migration depend sensitively on the mechanical properties of the extracellular matrix, yet substrate stiffness alone cannot account for the distinct behaviours observed on natural versus artificial materials. In this review, we synthesize experimental findings on cells interacting with collagen I matrices and viscoelastic hydrogels, and identify the key physical mechanisms that govern adhesion stability, turnover, and migratory efficiency. Collagen I substrates are characterized by structural anisotropy, spatial heterogeneity, and a broad spectrum of relaxation times, in contrast to the simplified and often isotropic response of artificial hydrogels. Based on these observations, we highlight the central role of interfacial slippage at the FA-substrate biointerface enabled by matrix remodelling and multi-timescale viscoelastic dissipation. We further discuss how cell-generated forces can induce collagen reorganization and surface tension gradients, potentially driving Marangoni-like flows that contribute to dynamic matrix redistribution. These processes collectively maintain adhesions in a state between stabilization and turnover, favourable for persistent migration. Finally, we consider the interplay between these mechanical mechanisms and mechanosensitive signalling, particularly involving Piezo1 ion channels. This perspective emphasizes that effective cell-matrix coupling arises from the ability of the substrate to dissipate and reorganize distribution of mechanical energy, rather than from stiffness alone.

Keywords:  Asymmetric wetting and de-wetting of focal adhesion; Collagen I substrates; Effects along the biointerface; Focal adhesion-substrate coupling; The Marangoni effect; Viscoelasticity

DOI:  https://doi.org/10.1007/s00249-026-01864-1
Cells. 2026 Aug 25. pii: 1531. [Epub ahead of print]15(17):

Viscotaxis: An Emerging Driver for Directed Cell Migration.

Zijian Chen, Zhen Wang, Guanglin Wang.

  Directed cell migration orchestrates embryonic development, wound repair, immune surveillance and malignant tumor invasion. Viscotaxis-directed cell migration along spatial gradients of extracellular fluid viscosity or matrix loss modulus-has emerged as a candidate mechanotaxis modality that may guide cells through heterogeneous viscoelastic tissues; however, its biological functions and molecular underpinnings remain largely uncharacterized, and direct evidence in mammalian systems is still limited to a small number of studies. This mini-review first defines viscotaxis and distinguishes it from the related but physically different mechanical quantities with which it is frequently conflated-substrate stiffness, matrix viscoelasticity, and stress relaxation-and then summarizes its physiological and pathological relevance across development, tissue homeostasis, immunity, and cancer. We outline the putative multi-step mechanosensory cascade governing viscotactic responses, examine how viscotaxis may synergize or compete with durotaxis, haptotaxis, chemotaxis, electrotaxis, and phototaxis under mixed microenvironmental cues, and compare the distinct hydrodynamic and steric-exclusion mechanisms proposed across spiral microbes, flagellated eukaryotes, mammalian cells, and embryonic tissues. Throughout, we explicitly distinguish evidence obtained under viscosity gradients from that obtained under uniformly elevated viscosity and established findings from working hypotheses. Finally, we discuss current methodological bottlenecks and unresolved conceptual debates and propose biomaterial tools and therapeutic strategies to advance viscotaxis from a biophysical curiosity toward a core principle of cellular mechanobiology.

Keywords:  cell mechanics; directed cell migration; viscoelasticity; viscotaxis

DOI:  https://doi.org/10.3390/cells15171531
Nat Methods. 2026 Sep 14.

CFM: confinement force microscopy-a dynamic, precise and stable microconfiner for traction force microscopy in spatial confinement.

Fatemeh Abbasi, Katharina Rieck, Matthias Brandt, Maja Matis, Eva Kiermaier, Timo Betz.

Cells migrating through tissues experience changing physical confinement, yet methods to dynamically control confinement while quantifying the resulting forces remain limited. Here we present a microconfiner platform for live-cell imaging that enables programmable confinement, allowing real-time control over the level, timing and frequency of confinement while measuring traction forces exerted on the microenvironment, a method we term confinement force microscopy (CFM). Using CFM, we find that cells respond to confinement in two phases: a rapid passive stress rise caused by compression of the cell body and nucleus against the substrate, followed by an active stress increase associated with enhanced contractility, intracellular pressure buildup and bleb formation. Bleb expansion can partially relieve pressure and reduce stress on the surroundings. ROCK and myosin II inhibition both reduce stress generation, but with distinct effects on blebbing. Overall, CFM provides a versatile approach to study dynamic mechanical adaptation in tissue-like environments.

DOI: https://doi.org/10.1038/s41592-026-03216-5
Front Cell Dev Biol. 2026 ;14 1900481

Crosslinker identity and dynamics regulate F-actin network structure and mechanics.

Lauren Godfrey, Bekele J Gurmessa.

  The coexistence of multiple actin crosslinking proteins in cells suggests that crosslinkers with distinct binding dynamics may cooperate to organize F-actin networks that support adhesion, motility, and division. Here, we examine how crosslinker identity and lifetime regulate actin-network structure and mechanics using a reconstituted system that combines α -actinin, a native dynamic actin crosslinker, with biotin-NeutrAvidin, a non-native model of long-lived, effectively persistent crosslinking. Using confocal fluorescence microscopy and optical-tweezers microrheology, we compared networks formed with α -actinin alone, biotin-NeutrAvidin alone, or a representative equimolar 50:50 mixture of the two crosslinking schemes at fixed total crosslinker-to-actin ratio, R . Mixed crosslinking produced the strongest mesoscale structural heterogeneity at high R , yielding larger characteristic structural features than either pure-crosslinker network. However, this structural coarsening did not translate into uniformly enhanced linear viscoelasticity: mixed networks generally exhibited moduli and viscosities intermediate between those of pure α -actinin and biotin-NeutrAvidin networks. Nonlinear microrheology further revealed that crosslinker identity and lifetime regulate force buildup, strain stiffening, and stress relaxation in an observable-dependent manner. Thus, the representative mixed-crosslinker network did not simply generate the strongest or most solid-like actin network. Instead, its effects were selective: it enhanced mesoscale heterogeneity at high R , produced intermediate linear and total nonlinear force responses, and gave rise to distinct nonlinear stiffening and relaxation behavior. These results demonstrate that cooperation between dynamic and persistent crosslinks is deformation-regime dependent, providing a mechanism for tuning actin-network architecture and mechanics without uniformly increasing rigidity.

Keywords:  F-actin networks; actin crosslinkers; biotin–NeutrAvidin; microrheology; nonlinear mechanics; stress relaxation; viscoelasticity; α-actinin

DOI:  https://doi.org/10.3389/fcell.2026.1900481
Adv Healthc Mater. 2026 Sep 15. e71724

Mechanically Active Biomaterials for Stem Cell Differentiation.

Lanxin Xu, Mingxia Lu, Hongxu Lu.

  Mechanical cues have emerged as critical regulators of stem cell fate, acting alongside biochemical signals to govern differentiation and functional maturation. In native tissues, stem cells reside within dynamic and mechanically heterogeneous microenvironments, where physical factors such as matrix stiffness, viscoelasticity, topography, and externally applied forces play essential roles in directing cellular behavior. Recent advances in mechanically active biomaterials have enabled precise control over the mechanical properties of stem cell microenvironments, providing powerful platforms to investigate mechanotransduction mechanisms and guide lineage specification. These materials-including stiffness-tunable and viscoelastic hydrogels, stimuli-responsive scaffolds, and dynamic culture systems-facilitate spatiotemporal modulation of mechanical cues and allow systematic interrogation of force-mediated signaling pathways, such as integrin-based adhesion, cytoskeletal remodeling, and YAP/TAZ-dependent transcriptional regulation. In this review, we summarize the fundamental mechanisms underlying mechanical regulation of stem cell differentiation and compare two- and three-dimensional culture systems from a mechanobiological perspective. We further highlight how material design principles can enhance functional maturation and translational relevance. Finally, we discuss current challenges and future opportunities in the development of scalable, clinically compatible mechanically active biomaterials. By integrating insights from mechanobiology and materials science, this review aims to provide design-oriented frameworks for the rational engineering of next-generation stem cell-based healthcare technologies.

Keywords:  biomaterials; dynamic mechanical stimulation; mechanical microenvironment; mechanotransduction; stem cell differentiation

DOI:  https://doi.org/10.1002/adhm.71724
Cell Biomater. 2026 Jul 03. pii: 100515. [Epub ahead of print]

Synthetic PEG-4MAL Hydrogels Support Patient-Derived Human Intestinal Enteroid Culture.

Luis F Arrieta-Viana, Maya L Zhang, Tatiana A Karakasheva, Kathryn E Hamilton, Andrés J García.

  Patient-derived intestinal enteroids are valuable models for studying gastrointestinal physiology and disease, but their dependence on Matrigel™ limits reproducibility and clinical translation. Here, we developed a fully synthetic poly(ethylene glycol)-4-maleimide (PEG-4MAL) hydrogel platform to support human intestinal enteroid culture. Guided by enteroid transcriptomics revealing high expression of α2β1 integrin and matrix metalloproteinases, we systematically evaluated collagen-mimetic GFOGER and fibronectin-derived RGD (Arg-Gly-Asp) peptides combined with four MMP-sensitive crosslinkers. GFOGER-functionalized hydrogels significantly outperformed RGD formulations across all metrics. The optimized PEG-4MAL-GFOGER formulation demonstrated enteroid formation efficiency and viability approaching Matrigel™ performance. Bulk RNA-sequencing across multiple patient-derived lines demonstrated transcriptomic similarity between synthetic and Matrigel™ hydrogels, with preservation of stem cell, differentiation, and regional identity markers. This rationally designed synthetic platform overcomes key limitations of biological matrices while supporting robust enteroid growth and functionality comparable to standard biological matrices.

Keywords:  cell adhesive peptides; intestinal organoids; matrix metalloproteinase-sensitive crosslinkers; synthetic hydrogels

DOI:  https://doi.org/10.1016/j.celbio.2026.100515
Matrix Biol Plus. 2026 Dec;32 100204

Fibronectin's tensional state as a mechanical signature of fibrotic extracellular matrix in idiopathic pulmonary fibrosis models.

Konstantin M P Wolf, Emmanouil Angelidakis, Daria Künzli, David Lauer, Matthias Brunner, Alessia Cambria, Divya Vats, Britta Maurer, Viola Vogel, Mamta Chabria.

  Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal disease with limited treatment options. Emerging evidence suggests that the composition and mechanics of the extracellular matrix (ECM) play a crucial role in IPF pathogenesis; however, biomarkers that indicate altered ECM signatures are scarce. To demonstrate a direct relationship between ECM fiber tension and fibrosis progression, we established an in vitro fibrosis assay using patient-derived fibroblasts and the tension-sensitive fibronectin-binding peptide FnBPA5, whose multivalent binding to fibronectin is impaired by fiber strain. The system was validated using known fibrosis biomarkers at the protein and mRNA levels. Loss of fibronectin fiber tension not only acts as a marker for fibrosis, but as shown here, tension can be restored upon treatment with antifibrotic drugs, concomitant with improved biomarker data. The loss of fibronectin fiber tension was further corroborated ex vivo by probing fibrotic lung cryosections from bleomycin-treated mice with FnBPA5. Taken together, our results highlight the mechanical state of fibronectin fibers as a promising biomarker for IPF.

Keywords:  Extracellular matrix; Fibronectin; Idiopathic pulmonary fibrosis; Mechanics

DOI:  https://doi.org/10.1016/j.mbplus.2026.100204
Biomacromolecules. 2026 Sep 14. 27(9): 6074-6085

Intrinsically Strain-Stiffening, Conductive, ROS-Scavenging Peptide-Polymer Hydrogel to Promote Neurite Outgrowth.

Debasish Nath, Jahanvi Ralhan, Pallavi S Chaubey, Manisha Nirwan, Asish Pal.

Neurodegenerative disorders pose a major global health challenge due to impaired electrical signaling in nerve fibers, yet effective regenerative therapies remain limited. Here, we report an injectable hydrogel that integrates intrinsic conductivity, antioxidative capacity, and strain-stiffening mechanics, to emulate key features of the neural extracellular matrix (ECM) and promote neuronal differentiation. We design peptide amphiphiles (Fcn, n = 5, 10) by anchoring a redox-active ferrocene (Fc) motif to a self-assembling peptide segment (NVFFAKKC) via methylene spacers (n). These nanofibers are dynamically cross-linked with a thermoresponsive polymer, PDMA, via Schiff-base chemistry to furnish Fcn-PDMA hydrogels exhibiting tunable electrical conductivity, potent radical-scavenging ability, and nonlinear strain-stiffening behavior. Notably, the hydrogels display both heat- and strain-induced stiffening behavior reminiscent of fibrin networks. In vitro experiments show that SH-SY5Y neuroblastoma cells encapsulated in these hydrogels, particularly Fc10-PDMA, exhibit excellent biocompatibility, resistance to oxidative stress, and enhanced neurite outgrowth. Taken together, the multifunctional hydrogels provide a biomimetic 3D niche that leverages electrical, mechanical, and redox cues to synergistically promote neurogenesis.

DOI: https://doi.org/10.1021/acs.biomac.6c00930