ArticleIntegrative biology : quantitative biosciences from nano to macro2015
Macrophage motility is driven by frontal-towing with a force magnitude dependent on substrate stiffness.
Article in Integrative biology : quantitative biosciences from nano to macro, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 70 citations in OpenAlex.
- An underlying mechanism of bovine mastitis: PGEThe veterinary quarterly · 2026Article
- Morpho-functional plasticity of tumour-associated macrophages: linking cell shape, ultrastructure, and immune regulation in cancer.Clinical and experimental medicine · 2026Review
- A novel role for TRPV1 in macrophage giant cell formation.bioRxiv : the preprint server for biology · 2026Article
- Trpv4-mediated mechanotransduction regulates the differentiation of valvular interstitial cells to myofibroblasts: implications for aortic valve stenosis.American journal of physiology. Cell physiology · 2025Article
- Macrophage microRNA-146a is a central regulator of the foreign body response to biomaterial implants.Biomaterials · 2025Article
- Inhibition of Mac-1 allows human macrophages to migrate against the direction of shear flow on ICAM-1.Molecular biology of the cell · 2024Article
- DNA methyltransferase 1 deficiency improves macrophage motility and wound healing by ameliorating cholesterol accumulation.NPJ Regenerative medicine · 2023Article
- Orthodontic Compression Enhances Macrophage M2 Polarization via Histone H3 Hyperacetylation.International journal of molecular sciences · 2023Article
- Not all (cells) who wander are lost: Upstream migration as a pervasive mode of amoeboid cell motility.Frontiers in cell and developmental biology · 2023Review
- Mechanosensitive Piezo1 protein as a novel regulator in macrophages and macrophage-mediated inflammatory diseases.Frontiers in immunology · 2023Review
- Extracellular matrix stiffness-The central cue for skin fibrosis.Frontiers in molecular biosciences · 2023Review
- Substrate stiffness reduces particle uptake by epithelial cells and macrophages in a size-dependent manner through mechanoregulation.Nanoscale · 2022Article
- Engineering physical microenvironments to study innate immune cell biophysics.APL bioengineering · 2022Review
- Mechanoimmunology: Are inflammatory epigenetic states of macrophages tuned by biophysical factors?APL bioengineering · 2022Review
- Role of mechanosensitive channels/receptors in atherosclerosis.American journal of physiology. Cell physiology · 2022Review
- Characterization of Macrophage and Cytokine Interactions with Biomaterials Used in Negative-Pressure Wound Therapy.Bioengineering (Basel, Switzerland) · 2021Article
- Inflammation Drives Stiffness Mediated Uptake of Lipoproteins in Primary Human Macrophages and Foam Cell Proliferation.Annals of biomedical engineering · 2021Article
- A Src-H3 acetylation signaling axis integrates macrophage mechanosensation with inflammatory response.Biomaterials · 2021Article
- Mechanosensing by TRPV4 mediates stiffness-induced foreign body response and giant cell formation.Science signaling · 2021Article
- Integrin cross-talk modulates stiffness-independent motility of CD4+ T lymphocytes.Molecular biology of the cell · 2021Article
Corrections and comments
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Authors and funding
3 authors at 3 institutions in 1 country.
Funding
Abstract
The ability of macrophages to properly migrate is crucial to their success as early responders during the innate immune response. Furthermore, improper regulation of macrophage migration is known to contribute to several pathologies. The signaling mechanisms underlying macrophage migration have been previously studied but to date the mechanical mechanism of macrophage migration has not been determined. In this study, we have created the first traction maps of motile primary human macrophages by observing their migration on compliant polyacrylamide gels. We find that the force generated by migrating macrophages is concentrated in the leading edge of the cell - so-called frontal towing - and that the magnitude of this force is dependent on the stiffness of the underlying matrix. With the aid of chemical inhibitors, we show that signaling through the RhoA kinase ROCK, myosin II, and PI3K is essential for proper macrophage force generation. Finally, we show that Rac activation by its GEF Vav1 is crucial for macrophage force generation while activation through its GEF Tiam1 is unnecessary.
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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.