Mammary epithelial morphogenesis in 3D combinatorial microenvironments

Abstract Human mammary epithelial cells can proliferate and reorganize into polarized multi-cellular constructs in-vitro, thereby functioning as an important model system in recapitulating key steps of in-vivo morphogenesis. Current approaches to constructing such three-dimensional mimics of the in-...

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Autores principales:	Raphaelle Luisier, Mehmet Girgin, Matthias P. Lutolf, Adrian Ranga
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/061c41c2313f4f678b24caa4dbe244d8
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spelling	oai:doaj.org-article:061c41c2313f4f678b24caa4dbe244d82021-12-02T16:18:03ZMammary epithelial morphogenesis in 3D combinatorial microenvironments10.1038/s41598-020-78432-w2045-2322https://doaj.org/article/061c41c2313f4f678b24caa4dbe244d82020-12-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-78432-whttps://doaj.org/toc/2045-2322Abstract Human mammary epithelial cells can proliferate and reorganize into polarized multi-cellular constructs in-vitro, thereby functioning as an important model system in recapitulating key steps of in-vivo morphogenesis. Current approaches to constructing such three-dimensional mimics of the in-vivo microenvironment have involved the use of complex and ill-defined naturally derived matrices, whose properties are difficult to manipulate independently, and which have therefore limited our ability to understand the extrinsic regulation of morphogenesis. Here, we employ an automated, high-throughput approach to array modular building blocks of synthetic components, and develop a systematic approach to analyze colonies resulting from these varied microenvironmental combinations. This methodology allows us to systematically map the relationship between microenvironmental properties and ensuing morphogenetic phenotypes. Our analysis reveals that apico-basal polarity of mammary epithelial cells occurs within a narrow range of matrix stiffness, and that phenotypic homogeneity is favored in matrices which are insensitive to MMP-mediated degradation. Furthermore, combinations of extracellular proteins in the matrix finely tune the morphology of the mammary colonies, suggesting that subtle disregulations of the microenvironment may play a significant role in pathological disease states. This approach, which leverages the combinatorial possibilities of modular synthetic artificial extracellular matrices with an automated technology platform, demonstrates how morphogenesis can be assessed systematically in 3D, and provides new insights into mammary epithelial multicellularity.Raphaelle LuisierMehmet GirginMatthias P. LutolfAdrian RangaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-10 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Raphaelle Luisier Mehmet Girgin Matthias P. Lutolf Adrian Ranga Mammary epithelial morphogenesis in 3D combinatorial microenvironments
description	Abstract Human mammary epithelial cells can proliferate and reorganize into polarized multi-cellular constructs in-vitro, thereby functioning as an important model system in recapitulating key steps of in-vivo morphogenesis. Current approaches to constructing such three-dimensional mimics of the in-vivo microenvironment have involved the use of complex and ill-defined naturally derived matrices, whose properties are difficult to manipulate independently, and which have therefore limited our ability to understand the extrinsic regulation of morphogenesis. Here, we employ an automated, high-throughput approach to array modular building blocks of synthetic components, and develop a systematic approach to analyze colonies resulting from these varied microenvironmental combinations. This methodology allows us to systematically map the relationship between microenvironmental properties and ensuing morphogenetic phenotypes. Our analysis reveals that apico-basal polarity of mammary epithelial cells occurs within a narrow range of matrix stiffness, and that phenotypic homogeneity is favored in matrices which are insensitive to MMP-mediated degradation. Furthermore, combinations of extracellular proteins in the matrix finely tune the morphology of the mammary colonies, suggesting that subtle disregulations of the microenvironment may play a significant role in pathological disease states. This approach, which leverages the combinatorial possibilities of modular synthetic artificial extracellular matrices with an automated technology platform, demonstrates how morphogenesis can be assessed systematically in 3D, and provides new insights into mammary epithelial multicellularity.
format	article
author	Raphaelle Luisier Mehmet Girgin Matthias P. Lutolf Adrian Ranga
author_facet	Raphaelle Luisier Mehmet Girgin Matthias P. Lutolf Adrian Ranga
author_sort	Raphaelle Luisier
title	Mammary epithelial morphogenesis in 3D combinatorial microenvironments
title_short	Mammary epithelial morphogenesis in 3D combinatorial microenvironments
title_full	Mammary epithelial morphogenesis in 3D combinatorial microenvironments
title_fullStr	Mammary epithelial morphogenesis in 3D combinatorial microenvironments
title_full_unstemmed	Mammary epithelial morphogenesis in 3D combinatorial microenvironments
title_sort	mammary epithelial morphogenesis in 3d combinatorial microenvironments
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/061c41c2313f4f678b24caa4dbe244d8
work_keys_str_mv	AT raphaelleluisier mammaryepithelialmorphogenesisin3dcombinatorialmicroenvironments AT mehmetgirgin mammaryepithelialmorphogenesisin3dcombinatorialmicroenvironments AT matthiasplutolf mammaryepithelialmorphogenesisin3dcombinatorialmicroenvironments AT adrianranga mammaryepithelialmorphogenesisin3dcombinatorialmicroenvironments
_version_	1718384213338619904

Mammary epithelial morphogenesis in 3D combinatorial microenvironments

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