bims-ecemfi 2026-04-26 papers

Acta Biomater. 2026 Apr 21. pii: S1742-7061(26)00251-5. [Epub ahead of print]

Hydrogel Viscoelasticity Regulates Human Monocyte-derived Macrophage Morphology and Phenotype in 2D Culture.

Consuelo Coser, Vincenzo di Bari, Amir M Ghaemmaghami, Jing Yang.

Macrophages are a key cell type in the foreign body reaction (FBR), playing a central role in the inflammatory response to implanted biomaterials and in fibrous capsule formation. However, the influence of biomaterial viscoelasticity on macrophages remains poorly understood. Only a very limited number of studies have investigated the viscoelastic-macrophage interactions, using cell lines or murine cells with ill-defined material viscoelasticity. Here, we investigated how hydrogels with tuneable viscoelasticity, featuring low initial moduli mimicking soft tissues mechanics and a stress relaxation timescale comparable to molecular clutch binding dynamics, modulate human monocyte-derived macrophage responses in 2D culture. Polyacrylamide (PAAm) hydrogels with comparable initial moduli, mesh size, chemistry and surface adsorbed proteins but distinct viscoelasticities were prepared by tuning monomer (acrylamide) and crosslinker (bisacrylamide) concentrations. While the elastic PAAm composition displayed minimal stress relaxation, the viscoelastic PAAm hydrogel showed pronounced stress relaxation with ∼70% decrease of its initial modulus within 5 minutes and τ1/2 ≈ 15.8 s (time to reach 50% of original modulus), a physiologically relevant timescale for cell-matrix binding dynamics and mechanotransduction. Human peripheral blood monocyte-derived macrophages cultured on the viscoelastic hydrogel spread more extensively and displayed higher eccentricity than those on elastic substrates. In contrast, macrophages on the elastic hydrogel showed reduced spreading, smaller cell area and increased clustering. Phenotype analysis revealed that elastic hydrogels promoted a pro-inflammatory response, characterised by elevated calprotectin expression and significantly higher secretion of TNF-α and IL-6, whereas anti-inflammatory surface markers and cytokines were not statistically different between the two hydrogel types. Collectively, these findings suggest that viscoelasticity is a key factor regulating macrophage phenotype, with effects dependent on initial modulus and stress relaxation rate, and highlight its relevance as a design parameter in immunomodulatory biomaterials with potential to mitigate the FBR. STATEMENT OF SIGNIFICANCE: This study reveals, for the first time, how viscoelastic hydrogels with physiologically relevant stress-relaxation timescales modulate the morphology and activation of human monocyte-derived macrophages. By engineering polyacrylamide hydrogels with comparable initial moduli, porosity and surface chemistry but distinct stress relaxation profiles, we isolated the specific contribution of viscoelasticity to macrophage mechanotransduction. Our findings demonstrate that substrate viscoelasticity critically governs macrophage morphology and inflammatory polarisation, with viscoelastic matrices attenuating pro-inflammation activation. This work bridges the gap between material mechanics and human macrophage polarisation, highlighting viscoelasticity as a tuneable design parameter for immunomodulatory biomaterials. These insights provide a foundation for developing next-generation implants and tissue scaffolds that leverage viscoelastic control to mitigate the foreign body response.

Keywords: Foreign Body Reaction; Human Macrophages; Immunomodulation; Stress Relaxation; Viscoelasticity

DOI: https://doi.org/10.1016/j.actbio.2026.04.032

Curr Opin Biomed Eng. 2025 Jun;pii: 100589. [Epub ahead of print]34

Interplay between extracellular matrix mechanics and cell function in mechanobiology.

Peter A Galie, Paul A Janmey.

Tissues are composites of cells and extracellular matrix that interact with each other both chemically and mechanically to form functioning organs with defined chemical and physical properties. Changes in the physical properties of the extracellular matrix often alter the function of cells, and reciprocally, modified cell function remodels the extracellular matrix in a complex iterative process that mediates normal development, wound healing, and pathological dysfunction. Recent advances in studying how cells and matrix physically interact with each other reveal new aspects of tissue and matrix mechanics and identify potential targets for therapeutic intervention in pathologic settings.

Keywords: Cell mechanics; Mechanotransduction; Viscoelasticity

DOI: https://doi.org/10.1016/j.cobme.2025.100589

PLoS Comput Biol. 2026 Apr 22. 22(4): e1014176

Phase-field modeling of border cell cluster migration in Drosophila.

Naghmeh Akhavan, Alexander George, Michelle Starz-Gaiano, Bradford E Peercy.

Collective cell migration is a fundamental biological process that drives events such as embryonic development, wound healing, and cancer metastasis. In this study, we develop a biophysically informed phase-field model to investigate the collective migration of the border cell cluster in the Drosophila melanogaster egg chamber. Our model captures key aspects of the egg chamber architecture, including the oocyte, nurse cells, and surrounding epithelium, and incorporates both mechanical forces and biochemical cues that guide cell migration. We introduce the Tangential Interface Migration (TIM) force which captures contact-mediated propulsion generated along interfaces between the border cell cluster and surrounding nurse cells. Our simulations reveal three key features of TIM-driven migration that distinguish it from previous forms of chemotaxis: (1) the explicit nature of border cell-nurse cell overlap to initiate movement (i.e., border cells cannot move without a nurse cell substrate), (2) motion is tangential to border cell-nurse cell interfaces, and (3) persistent migration occurs even in regions where the spatial slope of chemoattractant is decreasing. Additionally, we demonstrate that with or without geometry-mediated alterations in chemoattractant distribution such as at intercellular junctions, we can vary induced migration pauses, independent of mechanical confinement. We capture an experimentally observed transition to dorsal migration at the oocyte with a sustained medio-lateral chemical cue of small amplitude. The results show how spatial constraints and interfacial forces shape collective cell movement and highlight the utility of phase-field models in capturing the interplay between tissue geometry, contact forces, and chemical signaling.

DOI: https://doi.org/10.1371/journal.pcbi.1014176

Nat Cancer. 2026 Apr 20.

Heterogeneity and plasticity of cancer-associated fibroblasts.

Sneha Pramod, Hagar Lavon, Ruth Scherz-Shouval, Mara H Sherman.

Fibroblasts sense and respond to contextual cues to support tissue structure and function. In cancer, they engage a dysregulated wound-healing response that profoundly shapes tumor composition and progression. Efforts to therapeutically target these cancer-associated fibroblasts (CAFs) have been complicated by their heterogeneity and plasticity. However, recent advances, particularly in single-cell and spatial technologies, have greatly improved the understanding of the phenotypic consequences of distinct CAF states and functions. Here we review the current understanding of CAFs as heterogeneous, instructive regulators of tumor microenvironments across anatomic sites and highlight key challenges for the future.

DOI: https://doi.org/10.1038/s43018-026-01146-x

Macromolecules. 2026 Apr 14. 59(7): 4622-4635

Photoswitchable Cross-Linking in Polymer Gels: Effects on Surface Creasing and Network Relaxation during Swelling.

Alyssa VanZanten, Surbhi Punhani-Schillinger, M Reed Blocksome, Aditya Ketkar, Shih-Yuan Chen, Michelle M Driscoll, Robert C Ferrier, Caroline R Szczepanski.

Polymer gels with photoresponsive cross-links enable tunable mechanics and surface morphologies, making them promising for adaptive materials. While prior work on coumarin cross-linked gels has focused on photomediated events in dilute solution, their network-level mechanical responses remain unclear. Herein, we design PEG hydrogels with both permanent covalent and dynamic coumarin cross-links, allowing in situ modulation of cross-linking under wavelength-specific UV light. Real-time FTIR and dynamic mechanical analysis (DMA) show that postcure 365 nm irradiation drives rapid dimerization, increasing storage modulus by up to 69%, whereas cleavage of coumarin cross-links via 254 nm postcure irradiation has a more limited effect due to attenuation in bulk samples. Surface imaging reveals that dynamic cross-linking governs swelling-induced crease formation and evolution. Together, these results establish design principles for hydrogels with programmable mechanics and adaptive surface topographies, enabling light-addressable coatings, mechanically lockable soft actuators, and dynamic biomaterial interfaces.

DOI: https://doi.org/10.1021/acs.macromol.5c03103

Cell Rep Med. 2026 Apr 17. pii: S2666-3791(26)00168-0. [Epub ahead of print] 102751

Pan-cancer analysis of spatial transcriptomics reveals heterogeneous tumor spatial microenvironment.

Jiarong Li, Ping Lin, Heqi Wang, Zhixuan Tang, Xi Yan, Xufeng Chen, Jiao Yuan, Wanhong Chen, Hong Li.

Tumors are complex systems comprising diverse cell types that form the tumor spatial microenvironment (TSME). We present a pan-cancer spatial transcriptomic analysis of 373 samples across 12 cancer types and identify 56 local cellular programs (LCPs) and 13 recurrent niches. Ligand-receptor analysis reveals niche-shared and niche-specific interactions that drive spatial organization. Notably, gene expression in tumor cells and macrophages depends heavily on their specific location. Furthermore, niches associate significantly with clinical outcomes: macrophages colocalized with tumor cells (Niche_4) correlate with poor prognosis and immunotherapy resistance, while those colocalized with immune cells (Niche_11) predict better survival and treatment response. This systematic dissection of the TSME provides deeper insights into cellular communication and the structural influences governing complex tumor ecosystems.

Keywords: LR interaction; clinical implication; pan-cancer; spatial transcriptomics; tumor spatial microenvironment

DOI: https://doi.org/10.1016/j.xcrm.2026.102751