Extracellular matrix surface regulates self-assembly of three-dimensional placental trophoblast spheroids.

The incorporation of the extracellular matrix (ECM) is essential for generating in vitro models that truly represent the microarchitecture found in human tissues. However, the cell-cell and cell-ECM interactions in vitro remains poorly understood in placental trophoblast biology. We investigated the...

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Main Authors: Michael K Wong, Sarah A Shawky, Aditya Aryasomayajula, Madeline A Green, Tom Ewart, P Ravi Selvaganapathy, Sandeep Raha
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2018-01-01
Series:PLoS ONE
Online Access:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0199632&type=printable
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author Michael K Wong
Sarah A Shawky
Aditya Aryasomayajula
Madeline A Green
Tom Ewart
P Ravi Selvaganapathy
Sandeep Raha
author_facet Michael K Wong
Sarah A Shawky
Aditya Aryasomayajula
Madeline A Green
Tom Ewart
P Ravi Selvaganapathy
Sandeep Raha
author_sort Michael K Wong
collection DOAJ
description The incorporation of the extracellular matrix (ECM) is essential for generating in vitro models that truly represent the microarchitecture found in human tissues. However, the cell-cell and cell-ECM interactions in vitro remains poorly understood in placental trophoblast biology. We investigated the effects of varying the surface properties (surface thickness and stiffness) of two ECMs, collagen I and Matrigel, on placental trophoblast cell morphology, viability, proliferation, and expression of markers involved in differentiation/syncytial fusion. Most notably, thicker Matrigel surfaces were found to induce the self-assembly of trophoblast cells into 3D spheroids that exhibited thickness-dependent changes in viability, proliferation, syncytial fusion, and gene expression profiles compared to two-dimensional cultures. Changes in F-actin organization, cell spread morphologies, and integrin and matrix metalloproteinase gene expression profiles, further reveal that the response to surface thickness may be mediated in part through cellular stiffness-sensing mechanisms. Our derivation of self-assembling trophoblast spheroid cultures through regulation of ECM surface alone contributes to a deeper understanding of cell-ECM interactions, and may be important for the advancement of in vitro platforms for research or diagnostics.
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publishDate 2018-01-01
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spelling doaj-art-09a853f2e2874eeeb420e759c0135f252025-08-20T03:04:35ZengPublic Library of Science (PLoS)PLoS ONE1932-62032018-01-01136e019963210.1371/journal.pone.0199632Extracellular matrix surface regulates self-assembly of three-dimensional placental trophoblast spheroids.Michael K WongSarah A ShawkyAditya AryasomayajulaMadeline A GreenTom EwartP Ravi SelvaganapathySandeep RahaThe incorporation of the extracellular matrix (ECM) is essential for generating in vitro models that truly represent the microarchitecture found in human tissues. However, the cell-cell and cell-ECM interactions in vitro remains poorly understood in placental trophoblast biology. We investigated the effects of varying the surface properties (surface thickness and stiffness) of two ECMs, collagen I and Matrigel, on placental trophoblast cell morphology, viability, proliferation, and expression of markers involved in differentiation/syncytial fusion. Most notably, thicker Matrigel surfaces were found to induce the self-assembly of trophoblast cells into 3D spheroids that exhibited thickness-dependent changes in viability, proliferation, syncytial fusion, and gene expression profiles compared to two-dimensional cultures. Changes in F-actin organization, cell spread morphologies, and integrin and matrix metalloproteinase gene expression profiles, further reveal that the response to surface thickness may be mediated in part through cellular stiffness-sensing mechanisms. Our derivation of self-assembling trophoblast spheroid cultures through regulation of ECM surface alone contributes to a deeper understanding of cell-ECM interactions, and may be important for the advancement of in vitro platforms for research or diagnostics.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0199632&type=printable
spellingShingle Michael K Wong
Sarah A Shawky
Aditya Aryasomayajula
Madeline A Green
Tom Ewart
P Ravi Selvaganapathy
Sandeep Raha
Extracellular matrix surface regulates self-assembly of three-dimensional placental trophoblast spheroids.
PLoS ONE
title Extracellular matrix surface regulates self-assembly of three-dimensional placental trophoblast spheroids.
title_full Extracellular matrix surface regulates self-assembly of three-dimensional placental trophoblast spheroids.
title_fullStr Extracellular matrix surface regulates self-assembly of three-dimensional placental trophoblast spheroids.
title_full_unstemmed Extracellular matrix surface regulates self-assembly of three-dimensional placental trophoblast spheroids.
title_short Extracellular matrix surface regulates self-assembly of three-dimensional placental trophoblast spheroids.
title_sort extracellular matrix surface regulates self assembly of three dimensional placental trophoblast spheroids
url https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0199632&type=printable
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AT madelineagreen extracellularmatrixsurfaceregulatesselfassemblyofthreedimensionalplacentaltrophoblastspheroids
AT tomewart extracellularmatrixsurfaceregulatesselfassemblyofthreedimensionalplacentaltrophoblastspheroids
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