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ECM-transmitted shear stress induces apoptotic cell extrusion in early breast gland development

Epithelial cells of human breast glands are exposed to various mechanical ECM stresses that regulate tissue development and homeostasis. Mechanoadaptation of breast gland tissue to ECM-transmitted shear stress remained poorly investigated due to the lack of valid experimental approaches. Therefore,...

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Autores principales: Friedland, F., Babu, S., Springer, R., Konrad, J., Herfs, Y., Gerlach, S., Gehlen, J., Krause, H.-J., De Laporte, L., Merkel, R., Noetzel, E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9465044/
https://www.ncbi.nlm.nih.gov/pubmed/36105352
http://dx.doi.org/10.3389/fcell.2022.947430
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author Friedland, F.
Babu, S.
Springer, R.
Konrad, J.
Herfs, Y.
Gerlach, S.
Gehlen, J.
Krause, H.-J.
De Laporte, L.
Merkel, R.
Noetzel, E.
author_facet Friedland, F.
Babu, S.
Springer, R.
Konrad, J.
Herfs, Y.
Gerlach, S.
Gehlen, J.
Krause, H.-J.
De Laporte, L.
Merkel, R.
Noetzel, E.
author_sort Friedland, F.
collection PubMed
description Epithelial cells of human breast glands are exposed to various mechanical ECM stresses that regulate tissue development and homeostasis. Mechanoadaptation of breast gland tissue to ECM-transmitted shear stress remained poorly investigated due to the lack of valid experimental approaches. Therefore, we created a magnetic shear strain device that enabled, for the first time, to analyze the instant shear strain response of human breast gland cells. MCF10A-derived breast acini with basement membranes (BM) of defined maturation state and basoapical polarization were used to resemble breast gland morphogenesis in vitro. The novel biophysical tool was used to apply cyclic shear strain with defined amplitudes (≤15%, 0.2 Hz) over 22 h on living spheroids embedded in an ultrasoft matrix (<60 Pa). We demonstrated that breast spheroids gain resistance to shear strain, which increased with BM maturation and basoapical polarization. Most intriguingly, poorly developed spheroids were prone to cyclic strain-induced extrusion of apoptotic cells from the spheroid body. In contrast, matured spheroids were insensitive to this mechanoresponse—indicating changing mechanosensing or mechanotransduction mechanisms during breast tissue morphogenesis. Together, we introduced a versatile tool to study cyclic shear stress responses of 3D cell culture models. It can be used to strain, in principle, all kinds of cell clusters, even those that grow only in ultrasoft hydrogels. We believe that this approach opens new doors to gain new insights into dynamic shear strain-induced mechanobiological regulation circuits between cells and their ECM.
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spelling pubmed-94650442022-09-13 ECM-transmitted shear stress induces apoptotic cell extrusion in early breast gland development Friedland, F. Babu, S. Springer, R. Konrad, J. Herfs, Y. Gerlach, S. Gehlen, J. Krause, H.-J. De Laporte, L. Merkel, R. Noetzel, E. Front Cell Dev Biol Cell and Developmental Biology Epithelial cells of human breast glands are exposed to various mechanical ECM stresses that regulate tissue development and homeostasis. Mechanoadaptation of breast gland tissue to ECM-transmitted shear stress remained poorly investigated due to the lack of valid experimental approaches. Therefore, we created a magnetic shear strain device that enabled, for the first time, to analyze the instant shear strain response of human breast gland cells. MCF10A-derived breast acini with basement membranes (BM) of defined maturation state and basoapical polarization were used to resemble breast gland morphogenesis in vitro. The novel biophysical tool was used to apply cyclic shear strain with defined amplitudes (≤15%, 0.2 Hz) over 22 h on living spheroids embedded in an ultrasoft matrix (<60 Pa). We demonstrated that breast spheroids gain resistance to shear strain, which increased with BM maturation and basoapical polarization. Most intriguingly, poorly developed spheroids were prone to cyclic strain-induced extrusion of apoptotic cells from the spheroid body. In contrast, matured spheroids were insensitive to this mechanoresponse—indicating changing mechanosensing or mechanotransduction mechanisms during breast tissue morphogenesis. Together, we introduced a versatile tool to study cyclic shear stress responses of 3D cell culture models. It can be used to strain, in principle, all kinds of cell clusters, even those that grow only in ultrasoft hydrogels. We believe that this approach opens new doors to gain new insights into dynamic shear strain-induced mechanobiological regulation circuits between cells and their ECM. Frontiers Media S.A. 2022-08-29 /pmc/articles/PMC9465044/ /pubmed/36105352 http://dx.doi.org/10.3389/fcell.2022.947430 Text en Copyright © 2022 Friedland, Babu, Springer, Konrad, Herfs, Gerlach, Gehlen, Krause, De Laporte, Merkel and Noetzel. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cell and Developmental Biology
Friedland, F.
Babu, S.
Springer, R.
Konrad, J.
Herfs, Y.
Gerlach, S.
Gehlen, J.
Krause, H.-J.
De Laporte, L.
Merkel, R.
Noetzel, E.
ECM-transmitted shear stress induces apoptotic cell extrusion in early breast gland development
title ECM-transmitted shear stress induces apoptotic cell extrusion in early breast gland development
title_full ECM-transmitted shear stress induces apoptotic cell extrusion in early breast gland development
title_fullStr ECM-transmitted shear stress induces apoptotic cell extrusion in early breast gland development
title_full_unstemmed ECM-transmitted shear stress induces apoptotic cell extrusion in early breast gland development
title_short ECM-transmitted shear stress induces apoptotic cell extrusion in early breast gland development
title_sort ecm-transmitted shear stress induces apoptotic cell extrusion in early breast gland development
topic Cell and Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9465044/
https://www.ncbi.nlm.nih.gov/pubmed/36105352
http://dx.doi.org/10.3389/fcell.2022.947430
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