Cited by 82Cellular Mechanics and InteractionsSupramolecular Self-Assembly in MaterialsHydrogels: synthesis, properties, applications

Engineering strategies to recapitulate epithelial morphogenesis within synthetic three-dimensional extracellular matrix with tunable mechanical properties

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Miroshnikova, Y A, Jorgens, D M, Spirio, L, Auer, M, Sarang-Sieminski, A L, Weaver, V M·2011·Physical Biology

Abstract

The mechanical properties (e.g. stiffness) of the extracellular matrix (ECM) influence cell fate and tissue morphogenesis and contribute to disease progression. Nevertheless, our understanding of the mechanisms by which ECM rigidity modulates cell behavior and fate remains rudimentary. To address this issue, a number of two and three-dimensional (3D) hydrogel systems have been used to explore the effects of the mechanical properties of the ECM on cell behavior. Unfortunately, many of these systems have limited application because fiber architecture, adhesiveness and/or pore size often change in parallel when gel elasticity is varied. Here we describe the use of ECM-adsorbed, synthetic, self-assembling peptide (SAP) gels that are able to recapitulate normal epithelial acini morphogenesis and gene expression in a 3D context. By exploiting the range of viscoelasticity attainable with these SAP gels, and their ability to recreate native-like ECM fibril topology with minimal variability in ligand density and pore size, we were able to reconstitute normal and tumor-like phenotypes and gene expression patterns in nonmalignant mammary epithelial cells. Accordingly, this SAP hydrogel system presents the first tunable system capable of independently assessing the interplay between ECM stiffness and multi-cellular epithelial phenotype in a 3D context.

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  • The mechanical properties of Matrigel-based culture systems cannot be easily separated from their chemical cues.

    “The mechanical properties, such as elastic modulus, pore size, stress relaxation, and creep56–59, cannot be easily separated from the chemical cues in the Matrigel-based culture systems.”

    From Towards organoid culture without Matrigel (2021) · cites this paper as [59]

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  1. [77]Paszek MJ Tensional homeostasis and the malignant phenotype Cancer Cell 2005 8 3 241 54 16169468

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Authors
Miroshnikova, Y. A., Jorgens, D. M., Spirio, L., Auer, M., Sarang-Sieminski, A. L., & Weaver, V. M.
Affiliations
  • Franklin W. Olin College of Engineering (US)
  • Lawrence Berkeley National Laboratory (US)
  • University of California, San Francisco (US)
Corresponding author
Weaver, V M
Venue
Physical Biology
Published
2011-03-25
Volume
8
Issue
2
Pages
026013
ISSN
  • 1478-3967 (ISSN-L)
  • 1478-3975
OpenAlex
W2061300899
Cited by
82
References
96
Citations by year
2025: 3 · 2024: 4 · 2023: 5 · 2022: 4 · 2021: 14 · 2020: 4 · 2019: 3 · 2018: 2 · 2017: 4 · 2016: 8 · 2015: 7 · 2014: 7 · 2013: 10 · 2012: 5
FWCI
3.68
Type
journal article
Language
en
Open access
Locations
  • Physical Biology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Cancer Institute (R01CA138818, U54CA143836)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
  • Physical Sciences › Materials Science › Biomaterials › Supramolecular Self-Assembly in Materials
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Hydrogels: synthesis, properties, applications
Keywords
epithelial morphogenesis, extracellular matrix stiffness, self-assembling peptide hydrogel, synthetic extracellular matrix, viscoelasticity, mammary epithelial cells, acini formation, ligand density, pore size, 3D cell culture, tissue morphogenesis
MeSH terms
Biomechanical Phenomena, Epithelium, Extracellular Matrix, Humans, Morphogenesis, Peptides, Gene Expression, Porosity, Hydrogels, Tissue Engineering

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