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Synthetic matrices reveal contributions of ECM biophysical and biochemical properties to epithelial morphogenesis

Epithelial cells cultured within collagen and laminin gels proliferate to form hollow and polarized spherical structures, recapitulating the formation of a rudimentary epithelial organ. However, the contributions of extracellular matrix (ECM) biochemical and biophysical properties to morphogenesis a...

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Autores principales: Enemchukwu, Nduka O., Cruz-Acuña, Ricardo, Bongiorno, Tom, Johnson, Christopher T., García, José R., Sulchek, Todd, García, Andrés J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4700478/
https://www.ncbi.nlm.nih.gov/pubmed/26711502
http://dx.doi.org/10.1083/jcb.201506055
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author Enemchukwu, Nduka O.
Cruz-Acuña, Ricardo
Bongiorno, Tom
Johnson, Christopher T.
García, José R.
Sulchek, Todd
García, Andrés J.
author_facet Enemchukwu, Nduka O.
Cruz-Acuña, Ricardo
Bongiorno, Tom
Johnson, Christopher T.
García, José R.
Sulchek, Todd
García, Andrés J.
author_sort Enemchukwu, Nduka O.
collection PubMed
description Epithelial cells cultured within collagen and laminin gels proliferate to form hollow and polarized spherical structures, recapitulating the formation of a rudimentary epithelial organ. However, the contributions of extracellular matrix (ECM) biochemical and biophysical properties to morphogenesis are poorly understood because of uncontrolled presentation of multiple adhesive ligands, limited control over mechanical properties, and lot-to-lot compositional variability in these natural ECMs. We engineered synthetic ECM-mimetic hydrogels with independent control over adhesive ligand density, mechanical properties, and proteolytic degradation to study the impact of ECM properties on epithelial morphogenesis. Normal cyst growth, polarization, and lumen formation were restricted to a narrow range of ECM elasticity, whereas abnormal morphogenesis was observed at lower and higher elastic moduli. Adhesive ligand density dramatically regulated apicobasal polarity and lumenogenesis independently of cell proliferation. Finally, a threshold level of ECM protease degradability was required for apicobasal polarity and lumen formation. This synthetic ECM technology provides new insights into how cells transduce ECM properties into complex morphogenetic behaviors.
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spelling pubmed-47004782016-07-04 Synthetic matrices reveal contributions of ECM biophysical and biochemical properties to epithelial morphogenesis Enemchukwu, Nduka O. Cruz-Acuña, Ricardo Bongiorno, Tom Johnson, Christopher T. García, José R. Sulchek, Todd García, Andrés J. J Cell Biol Research Articles Epithelial cells cultured within collagen and laminin gels proliferate to form hollow and polarized spherical structures, recapitulating the formation of a rudimentary epithelial organ. However, the contributions of extracellular matrix (ECM) biochemical and biophysical properties to morphogenesis are poorly understood because of uncontrolled presentation of multiple adhesive ligands, limited control over mechanical properties, and lot-to-lot compositional variability in these natural ECMs. We engineered synthetic ECM-mimetic hydrogels with independent control over adhesive ligand density, mechanical properties, and proteolytic degradation to study the impact of ECM properties on epithelial morphogenesis. Normal cyst growth, polarization, and lumen formation were restricted to a narrow range of ECM elasticity, whereas abnormal morphogenesis was observed at lower and higher elastic moduli. Adhesive ligand density dramatically regulated apicobasal polarity and lumenogenesis independently of cell proliferation. Finally, a threshold level of ECM protease degradability was required for apicobasal polarity and lumen formation. This synthetic ECM technology provides new insights into how cells transduce ECM properties into complex morphogenetic behaviors. The Rockefeller University Press 2016-01-04 /pmc/articles/PMC4700478/ /pubmed/26711502 http://dx.doi.org/10.1083/jcb.201506055 Text en © 2016 Enemchukwu et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
spellingShingle Research Articles
Enemchukwu, Nduka O.
Cruz-Acuña, Ricardo
Bongiorno, Tom
Johnson, Christopher T.
García, José R.
Sulchek, Todd
García, Andrés J.
Synthetic matrices reveal contributions of ECM biophysical and biochemical properties to epithelial morphogenesis
title Synthetic matrices reveal contributions of ECM biophysical and biochemical properties to epithelial morphogenesis
title_full Synthetic matrices reveal contributions of ECM biophysical and biochemical properties to epithelial morphogenesis
title_fullStr Synthetic matrices reveal contributions of ECM biophysical and biochemical properties to epithelial morphogenesis
title_full_unstemmed Synthetic matrices reveal contributions of ECM biophysical and biochemical properties to epithelial morphogenesis
title_short Synthetic matrices reveal contributions of ECM biophysical and biochemical properties to epithelial morphogenesis
title_sort synthetic matrices reveal contributions of ecm biophysical and biochemical properties to epithelial morphogenesis
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4700478/
https://www.ncbi.nlm.nih.gov/pubmed/26711502
http://dx.doi.org/10.1083/jcb.201506055
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