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Mechanosensing regulates tissue repair program in macrophages

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Meizlish, Matthew L., Kimura, Yoshitaka, Pope, Scott D., Matta, Rita, Kim, Catherine, Philip, Naomi H., Meyaard, Linde, Gonzalez, Anjelica +1 more·2024·Science Advances
DOI 10.1126/sciadv.adk6906PMC PMC10936955
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Abstract

Tissue-resident macrophages play important roles in tissue homeostasis and repair. However, how macrophages monitor and maintain tissue integrity is not well understood. The extracellular matrix (ECM) is a key structural and organizational component of all tissues. Here, we find that macrophages sense the mechanical properties of the ECM to regulate a specific tissue repair program. We show that macrophage mechanosensing is mediated by cytoskeletal remodeling and can be performed in three-dimensional environments through a noncanonical, integrin-independent mechanism analogous to amoeboid migration. We find that these cytoskeletal dynamics also integrate biochemical signaling by colony-stimulating factor 1 and ultimately regulate chromatin accessibility to control the mechanosensitive gene expression program. This study identifies an "amoeboid" mode of ECM mechanosensing through which macrophages may regulate tissue repair and fibrosis.

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  • The mechanosensitive channel Piezo1 directly senses matrix stiffness.

    “The mechanosensitive channel Piezo1 has been demonstrated to directly sense matrix stiffness (14).”

    From Matrix mechanical remodeled carrier-free nanosystem for programmable closed-loop reversal of liver fibrosis via STING alkylation (2025) · cites this paper as [14]

    The Introduction (page unavailable) says there is evidence that PIEZO1 is involved in sensing substrate stiffness on 2D surfaces, but it does not establish that PIEZO1 directly senses matrix stiffness. The Results (page unavailable) further report that deleting PIEZO1 did not affect the measured macrophage response in 3D collagen gels. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

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References 94 · Cited by 114

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Authors
Meizlish, M. L., Kimura, Y., Pope, S. D., Matta, R., Kim, C., Philip, N. H., Meyaard, L., Gonzalez, A., & Medzhitov, R.
Affiliations
  • Yale University (US)
  • Utrecht University (NL)
  • Howard Hughes Medical Institute (US)
Corresponding author
  • Meizlish, Matthew L.
  • Kimura, Yoshitaka
  • Medzhitov, Ruslan
ORCID
Venue
Science Advances
Publisher
American Association for the Advancement of Science (AAAS)
Published
2024-03-15
Volume
10
Issue
11
Pages
eadk6906-eadk6906
ISSN
2375-2548 (ISSN-L)
DOI
10.1126/sciadv.adk6906
PMC
PMC10936955
OpenAlex
W4392746957
Cited by
114
References
94
Citations by year
2026: 61 · 2025: 42 · 2024: 11
FWCI
25.63
Type
journal article
Language
en
Open access
Licence
cc-by-nc
Locations
  • Science Advances (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Utrecht University Repository (Utrecht University) (submittedVersion, other-oa)
Funders
  • Yale University
  • Washington University in St. Louis
  • Institute of Science and Technology Austria
  • University of Leicester
  • University of California, Los Angeles
  • National Heart, Lung, and Blood Institute (F31HL139116)
  • National Institute of General Medical Sciences (T32GM136651, T32GM086287)
  • National Institute of Allergy and Infectious Diseases (R01AI144152)
  • National Institute of Diabetes and Digestive and Kidney Diseases (P30DK034989)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
  • Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
  • Health Sciences › Medicine › Rehabilitation › Wound Healing and Treatments
Keywords
extracellular matrix mechanics, tissue repair, cytoskeletal remodeling, amoeboid migration, colony-stimulating factor 1, chromatin accessibility, gene expression regulation, fibrosis, tissue homeostasis
MeSH terms
Cytoskeleton, Extracellular Matrix, Macrophages, Signal Transduction, Integrins

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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