Inherent interfacial mechanical gradients in 3D hydrogels influence tumor cell behaviors.

Cells sense and respond to the rigidity of their microenvironment by altering their morphology and migration behavior. To examine this response, hydrogels with a range of moduli or mechanical gradients have been developed. Here, we show that edge effects inherent in hydrogels supported on rigid subs...

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Autores principales: Shreyas S Rao, Sarah Bentil, Jessica DeJesus, John Larison, Alex Hissong, Rebecca Dupaix, Atom Sarkar, Jessica O Winter
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Publicado: Public Library of Science (PLoS) 2012
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Acceso en línea:https://doaj.org/article/8a7b3c4efca849ed88427e8140783a73
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spelling oai:doaj.org-article:8a7b3c4efca849ed88427e8140783a732021-11-18T07:20:54ZInherent interfacial mechanical gradients in 3D hydrogels influence tumor cell behaviors.1932-620310.1371/journal.pone.0035852https://doaj.org/article/8a7b3c4efca849ed88427e8140783a732012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22558241/?tool=EBIhttps://doaj.org/toc/1932-6203Cells sense and respond to the rigidity of their microenvironment by altering their morphology and migration behavior. To examine this response, hydrogels with a range of moduli or mechanical gradients have been developed. Here, we show that edge effects inherent in hydrogels supported on rigid substrates also influence cell behavior. A Matrigel hydrogel was supported on a rigid glass substrate, an interface which computational techniques revealed to yield relative stiffening close to the rigid substrate support. To explore the influence of these gradients in 3D, hydrogels of varying Matrigel content were synthesized and the morphology, spreading, actin organization, and migration of glioblastoma multiforme (GBM) tumor cells were examined at the lowest (<50 µm) and highest (>500 µm) gel positions. GBMs adopted bipolar morphologies, displayed actin stress fiber formation, and evidenced fast, mesenchymal migration close to the substrate, whereas away from the interface, they adopted more rounded or ellipsoid morphologies, displayed poor actin architecture, and evidenced slow migration with some amoeboid characteristics. Mechanical gradients produced via edge effects could be observed with other hydrogels and substrates and permit observation of responses to multiple mechanical environments in a single hydrogel. Thus, hydrogel-support edge effects could be used to explore mechanosensitivity in a single 3D hydrogel system and should be considered in 3D hydrogel cell culture systems.Shreyas S RaoSarah BentilJessica DeJesusJohn LarisonAlex HissongRebecca DupaixAtom SarkarJessica O WinterPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 4, p e35852 (2012)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Shreyas S Rao
Sarah Bentil
Jessica DeJesus
John Larison
Alex Hissong
Rebecca Dupaix
Atom Sarkar
Jessica O Winter
Inherent interfacial mechanical gradients in 3D hydrogels influence tumor cell behaviors.
description Cells sense and respond to the rigidity of their microenvironment by altering their morphology and migration behavior. To examine this response, hydrogels with a range of moduli or mechanical gradients have been developed. Here, we show that edge effects inherent in hydrogels supported on rigid substrates also influence cell behavior. A Matrigel hydrogel was supported on a rigid glass substrate, an interface which computational techniques revealed to yield relative stiffening close to the rigid substrate support. To explore the influence of these gradients in 3D, hydrogels of varying Matrigel content were synthesized and the morphology, spreading, actin organization, and migration of glioblastoma multiforme (GBM) tumor cells were examined at the lowest (<50 µm) and highest (>500 µm) gel positions. GBMs adopted bipolar morphologies, displayed actin stress fiber formation, and evidenced fast, mesenchymal migration close to the substrate, whereas away from the interface, they adopted more rounded or ellipsoid morphologies, displayed poor actin architecture, and evidenced slow migration with some amoeboid characteristics. Mechanical gradients produced via edge effects could be observed with other hydrogels and substrates and permit observation of responses to multiple mechanical environments in a single hydrogel. Thus, hydrogel-support edge effects could be used to explore mechanosensitivity in a single 3D hydrogel system and should be considered in 3D hydrogel cell culture systems.
format article
author Shreyas S Rao
Sarah Bentil
Jessica DeJesus
John Larison
Alex Hissong
Rebecca Dupaix
Atom Sarkar
Jessica O Winter
author_facet Shreyas S Rao
Sarah Bentil
Jessica DeJesus
John Larison
Alex Hissong
Rebecca Dupaix
Atom Sarkar
Jessica O Winter
author_sort Shreyas S Rao
title Inherent interfacial mechanical gradients in 3D hydrogels influence tumor cell behaviors.
title_short Inherent interfacial mechanical gradients in 3D hydrogels influence tumor cell behaviors.
title_full Inherent interfacial mechanical gradients in 3D hydrogels influence tumor cell behaviors.
title_fullStr Inherent interfacial mechanical gradients in 3D hydrogels influence tumor cell behaviors.
title_full_unstemmed Inherent interfacial mechanical gradients in 3D hydrogels influence tumor cell behaviors.
title_sort inherent interfacial mechanical gradients in 3d hydrogels influence tumor cell behaviors.
publisher Public Library of Science (PLoS)
publishDate 2012
url https://doaj.org/article/8a7b3c4efca849ed88427e8140783a73
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AT sarahbentil inherentinterfacialmechanicalgradientsin3dhydrogelsinfluencetumorcellbehaviors
AT jessicadejesus inherentinterfacialmechanicalgradientsin3dhydrogelsinfluencetumorcellbehaviors
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AT alexhissong inherentinterfacialmechanicalgradientsin3dhydrogelsinfluencetumorcellbehaviors
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