ArticleNature materials2018
Spatial confinement downsizes the inflammatory response of macrophages.
Article in Nature materials, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 141 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
141 citing papers in PubMed, 1 synthesis or guideline pooled it, 267 citations in OpenAlex.
- Mechanical stress-mediated immune and inflammatory regulation:Frontiers in medicine · 2025Pooled it
- Nuclear mechanotransduction: tools for mechanical perturbation and chromatin characterization.Nucleus (Austin, Tex.) · 2026Review
- Nuclear mechanobiology: a brief history and five unresolved questions.Nucleus (Austin, Tex.) · 2026Article
- MAP Crosslinker Chirality Regulates Macrophage Polarization Through MD-2 Engagement and Enables Tunable Immunomodulation Through Novel Peptide Design.Advanced healthcare materials · 2026Article
- Real-Time Scanning Ion Conductance Microscopy Reveals MARCKS-Driven Morphological Remodeling and Nanomechanical Softening during LPS-Induced Macrophage Polarization.Analytical chemistry · 2026Article
- Cell-Type-Tailored Hydrogels for Adoptive Cell Therapy in Cancer.Gels (Basel, Switzerland) · 2026Review
- Dental implant nanotopography for peri-implant tissue stability: soft-tissue sealing, innate immune calibration, and active biointerface regulation.International journal of implant dentistry · 2026Review
- Mechano-reprogramming of tumor-associated macrophages by engineering nanogel stiffness for suppression of tumor development.Journal of nanobiotechnology · 2026Article
- Immunomodulatory topographies regulate myofibroblast differentiation and influence fibrous encapsulation of glaucoma drainage devices.Bioactive materials · 2026Article
- Biochemical signals from the extracellular matrix in inflammation and tumour immunology.Nature reviews. Immunology · 2026Review
- A customizable, low-cost 3D-printed device for live cell confinement imaging.Lab on a chip · 2026Article
- Idiopathic pulmonary fibrosis from a multiscale mechanobiology perspective: Mechanisms and future therapeutic prospects.iScience · 2026Review
- Mechanical communication and function regulation of immune cells.Fundamental research · 2026Review
- Astroimmunology: the effects of spaceflight and its associated stressors on the immune system.Nature reviews. Immunology · 2026Review
- Matrix Stiffness Governs Fibroblasts' Regulation of Gingival Immune Homeostasis.Advanced materials (Deerfield Beach, Fla.) · 2026Article
- Mechanobiological regulation of T cellsLab on a chip · 2026Article
- Macrophage polarization state influences fusion and phenotype of human foreign body giant cellsFrontiers in immunology · 2026Article
- Geometric mechanogenomics: engineering boundary conditions for deterministic cell fate control.Frontiers in cell and developmental biology · 2026Review
- Particle Shape Modulates the Function of Adoptive Macrophage Transfers.Advanced healthcare materials · 2025Article
- Matrix Stiffness Governs Fibroblast-Driven Immune Homeostasis in Gingival Tissues.bioRxiv : the preprint server for biology · 2025Article
81 more citing papers are in PubMed but not listed here.
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2 authors at 1 institution in 1 country.
Funding
Abstract
Macrophages respond to chemical/metabolic and physical stimuli, but their effects cannot be readily decoupled in vivo during pro-inflammatory activation. Here, we show that preventing macrophage spreading by spatial confinement, as imposed by micropatterning, microporous substrates or cell crowding, suppresses late lipopolysaccharide (LPS)-activated transcriptional programs (biomarkers IL-6, CXCL9, IL-1β, and iNOS) by mechanomodulating chromatin compaction and epigenetic alterations (HDAC3 levels and H3K36-dimethylation). Mechanistically, confinement reduces actin polymerization, thereby lowers the LPS-stimulated nuclear translocation of MRTF-A. This lowers the activity of the MRTF-A-SRF complex and subsequently downregulates the inflammatory response, as confirmed by chromatin immunoprecipitation coupled with quantitative PCR and RNA sequencing analysis. Confinement thus downregulates pro-inflammatory cytokine secretion and, well before any activation processes, the phagocytic potential of macrophages. Contrarily, early events, including activation of the LPS receptor TLR4, and downstream NF-κB and IRF3 signalling and hence the expression of early LPS-responsive genes were marginally affected by confinement. These findings have broad implications in the context of mechanobiology, inflammation and immunology, as well as in tissue engineering and regenerative medicine.
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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 OpenQuestion graph.