ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2025
Matrix-Rigidity Cooperates With Biochemical Cues in M2 Macrophage Activation Through Increased Nuclear Deformation and Chromatin Accessibility.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- Mechanobiology of orofacial tissues: principles, mechanisms, and therapeutic applications.International journal of oral science · 2026Review
- Unraveling the epigenetic code in cancer cell-tumor microenvironment crosstalk.Molecular oncology · 2026Review
- Nanomedicine targeting ECM stiffness: restoring mechanical homeostasis for cancer immunotherapy.Materials today. Bio · 2026Review
- Application of hydrogels in 3D tumor microenvironment modeling and drug screening for cervical cancer: A review.Bioengineering & translational medicine · 2026Review
- IL4I1+ macrophages drive hepatocellular carcinoma progression by responding to biomechanical cues.JHEP reports : innovation in hepatology · 2026Article
- Recent advances in immunoregulatory biomaterials for tendon healing: From immune remodeling to functional regeneration.Materials today. Bio · 2026Review
- Sprayable nanozyme hydrogel epigenetically remodels inflammation for diabetic wound regeneration.Nature communications · 2026Article
- Hemodynamics and matrix stiffness shape the pathogenicity of SPP1Frontiers in immunology · 2026Review
- The mechano-immunological barrier in fibrosis-associated lung cancer: targeting matrix stiffness and the Piezo1 axis for microenvironment normalization.Frontiers in pharmacology · 2026Review
- Temporal Stretch-Induced Nuclear Mechanosensing Coordinates Early Chromatin Accessibility and Genome Protection.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Mechanical Microenvironment in Tumor Immune Evasion: Bidirectional Regulation Between Matrix Stiffness and Immune Cells and Its Therapeutic Implications.International journal of biological sciences · 2026Review
- Polarization increases nuclear stiffness in macrophages despite reduction in lamin A/C levels.npj biological physics and mechanics · 2026Article
- Matrix-Rigidity Cooperates With Biochemical Cues in M2 Macrophage Activation Through Increased Nuclear Deformation and Chromatin Accessibility.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
Corrections and comments
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Authors and funding
12 authors.
Funding
Abstract
Macrophages encounter a myriad of biochemical and mechanical stimuli across various tissues and pathological contexts. Notably, matrix rigidity has emerged as a pivotal regulator of macrophage activation through mechanotransduction. However, the precise mechanisms underlying the interplay between mechanical and biochemical cues within the nuclear milieu remain elusive. Here We elucidate how the increased matrix rigidity drives macrophages to amplify alternatively-activated (M2 phenotype) signaling cooperatively with biochemical cues (e.g., IL4/13) through altered nuclear mechanics. We demonstrate that reconstructed podosome-like F-actins and contractility induce nucleus deformation, opening nuclear pores, which facilitates nuclear translocation of the key transcription factor STAT6. Furthermore, the altered nuclear mechanics increases chromatin accessibility induced by H3K9 methylation, particularly of M2-associated gene promoters. These cooperative events of the mechano-chemical signaling at the cytoskeletal-to-nuclear domains facilitate M2 transcriptional activation and cellular functions. We further evidence the rigidity-primed M2 macrophages are immunosuppressive and accumulated within stiffened tumors in patients. This study proposes a mechanism by which matrix mechanics crosstalks with biochemical signals to potentiate macrophage activation through nuclear mechanosensing and chromatin modifications, offering insights into macrophage mechanobiology and its therapeutic modulations.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.