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Cited by 102Cellular Mechanics and InteractionsElasticity and Material Modeling3D Printing in Biomedical Research

Mechanical plasticity of collagen directs branch elongation in human mammary gland organoids

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Buchmann, B., Engelbrecht, L. K., Fernandez, P., Hutterer, F. P., Raich, M. K., Scheel, C. H., Bausch, A. R.·2021·Nature Communications
DOI 10.1038/s41467-021-22988-2PMC PMC8115695
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Abstract

Epithelial branch elongation is a central developmental process during branching morphogenesis in diverse organs. This fundamental growth process into large arborized epithelial networks is accompanied by structural reorganization of the surrounding extracellular matrix (ECM), well beyond its mechanical linear response regime. Here, we report that epithelial ductal elongation within human mammary organoid branches relies on the non-linear and plastic mechanical response of the surrounding collagen. Specifically, we demonstrate that collective back-and-forth motion of cells within the branches generates tension that is strong enough to induce a plastic reorganization of the surrounding collagen network which results in the formation of mechanically stable collagen cages. Such matrix encasing in turn directs further tension generation, branch outgrowth and plastic deformation of the matrix. The identified mechanical tension equilibrium sets a framework to understand how mechanical cues can direct ductal branch elongation.

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  • Many other organoid models, including brain, intestinal, mammary gland, and retinal organoids, employ 3D ECM-based hydrogels to induce complex tissue architecture that cannot be achieved in ECM-free floating culture.

    “While many other organoid models, including brain[13], intestinal [14], mammary gland [15], and retinal organoids [16], employ 3D ECM-based hydrogels to induce complex tissue architecture that cannot be achieved in ECM-free floating culture, the same has not been explored for skin yet.”

    From Efficient Generation of Skin Organoids from Pluripotent Cells via Defined Extracellular Matrix Cues and Morphogen Gradients in a Spindle‐Shaped Microfluidic Device (2024) · cites this paper as [15]

    The Results section reports that human mammary organoids grown in freely floating collagen I gels develop branches and mammary-like bilayered architecture. This supports the mammary-organoid example, but the paper does not establish that such architecture cannot be achieved in ECM-free floating culture. The other organoid types have separate citations in the citing sentence. (LLM, conf=0.84)

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References 50 · Cited by 102

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Authors
Buchmann, B., Engelbrecht, L. K., Fernandez, P., Hutterer, F. P., Raich, M. K., Scheel, C. H., & Bausch, A. R.
Affiliations
  • Technical University of Munich (DE)
  • Helmholtz Munich (DE)
Corresponding author
  • Scheel, C. H.
  • Bausch, A. R.
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2021-05-12
Volume
12
Issue
1
Pages
2759-2759
ISSN
2041-1723 (ISSN-L)
DOI
10.1038/s41467-021-22988-2
PMC
PMC8115695
OpenAlex
W3162491164
Cited by
102
References
50
Citations by year
2026: 15 · 2025: 31 · 2024: 11 · 2023: 21 · 2022: 16 · 2021: 8
FWCI
7.31
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Communications (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • PuSH - Publication Server of Helmholtz Zentrum München (submittedVersion, cc-by)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • mediaTUM – the media and publications repository of the Technical University Munich (Technical University Munich) (submittedVersion, other-oa)
  • Site cant be reached (submittedVersion, cc-by)
Funders
  • European Commission (HORIZON2020, 201269156, 810104)
  • Deutsche Forschungsgemeinschaft (SFB1032,, 201269156)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
  • Physical Sciences › Engineering › Biomedical Engineering › Elasticity and Material Modeling
  • Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
Keywords
branching morphogenesis, extracellular matrix mechanics, mechanical tension, collective cell migration
MeSH terms
Cell Movement, Collagen, Epithelial Cells, Extracellular Matrix, Humans, Morphogenesis, Organoids, Mammary Glands, Human, Biophysical Phenomena

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