Engineering strategies to recapitulate epithelial morphogenesis within synthetic three-dimensional extracellular matrix with tunable mechanical properties
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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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- 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
- Publisher
- IOP Publishing
- Published
- 2011-03-25
- Volume
- 8
- Issue
- 2
- Pages
- 026013
- ISSN
- 1478-3967 (ISSN-L)
- 1478-3975
- PMC
- PMC3401181
- 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
- green
- www.ncbi.nlm.nih.gov
- 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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