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

TitleEngineering strategies to recapitulate epithelial morphogenesis within synthetic three-dimensional extracellular matrix with tunable mechanical properties.
Publication TypeJournal Article
Year of Publication2011
AuthorsMiroshnikova YA, Jorgens DM, Spirio L, Auer M, Sarang-Sieminski AL, Weaver VM
JournalPhys Biol
Volume8
Issue2
Pagination026013
Date Published2011 Apr
ISSN1478-3975
KeywordsBiomechanical Phenomena, Epithelium, Extracellular Matrix, Gene Expression, Humans, Hydrogels, Morphogenesis, Peptides, Porosity, Tissue Engineering
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.

DOI10.1088/1478-3975/8/2/026013
Alternate JournalPhys Biol
PubMed ID21441648
PubMed Central IDPMC3401181
Grant List5R01CA138818-02 / CA / NCI NIH HHS / United States
R01 CA138818 / CA / NCI NIH HHS / United States
R01 CA138818-01A1 / CA / NCI NIH HHS / United States
R01 CA138818-02 / CA / NCI NIH HHS / United States
R01 CA138818-03 / CA / NCI NIH HHS / United States
U54 CA143836 / CA / NCI NIH HHS / United States
U54CA143836-01 / CA / NCI NIH HHS / United States