Deciphering the combinatorial roles of geometric, mechanical, and adhesion cues in regulation of cell spreading.

Significant effort has gone towards parsing out the effects of surrounding microenvironment on macroscopic behavior of stem cells. Many of the microenvironmental cues, however, are intertwined, and thus, further studies are warranted to identify the intricate interplay among the conflicting downstre...

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Main Authors: Greg M Harris, Tarek Shazly, Ehsan Jabbarzadeh
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2013-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC3839898?pdf=render
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author Greg M Harris
Tarek Shazly
Ehsan Jabbarzadeh
author_facet Greg M Harris
Tarek Shazly
Ehsan Jabbarzadeh
author_sort Greg M Harris
collection DOAJ
description Significant effort has gone towards parsing out the effects of surrounding microenvironment on macroscopic behavior of stem cells. Many of the microenvironmental cues, however, are intertwined, and thus, further studies are warranted to identify the intricate interplay among the conflicting downstream signaling pathways that ultimately guide a cell response. In this contribution, by patterning adhesive PEG (polyethylene glycol) hydrogels using Dip Pen Nanolithography (DPN), we demonstrate that substrate elasticity, subcellular elasticity, ligand density, and topography ultimately define mesenchymal stem cells (MSCs) spreading and shape. Physical characteristics are parsed individually with 7 kilopascal (kPa) hydrogel islands leading to smaller, spindle shaped cells and 105 kPa hydrogel islands leading to larger, polygonal cell shapes. In a parallel effort, a finite element model was constructed to characterize and confirm experimental findings and aid as a predictive tool in modeling cell microenvironments. Signaling pathway inhibition studies suggested that RhoA is a key regulator of cell response to the cooperative effect of the tunable substrate variables. These results are significant for the engineering of cell-extra cellular matrix interfaces and ultimately decoupling matrix bound cues presented to cells in a tissue microenvironment for regenerative medicine.
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spelling doaj.art-0141d97ed9c84b4199314ef5ab491af02022-12-22T01:58:08ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-01811e8111310.1371/journal.pone.0081113Deciphering the combinatorial roles of geometric, mechanical, and adhesion cues in regulation of cell spreading.Greg M HarrisTarek ShazlyEhsan JabbarzadehSignificant effort has gone towards parsing out the effects of surrounding microenvironment on macroscopic behavior of stem cells. Many of the microenvironmental cues, however, are intertwined, and thus, further studies are warranted to identify the intricate interplay among the conflicting downstream signaling pathways that ultimately guide a cell response. In this contribution, by patterning adhesive PEG (polyethylene glycol) hydrogels using Dip Pen Nanolithography (DPN), we demonstrate that substrate elasticity, subcellular elasticity, ligand density, and topography ultimately define mesenchymal stem cells (MSCs) spreading and shape. Physical characteristics are parsed individually with 7 kilopascal (kPa) hydrogel islands leading to smaller, spindle shaped cells and 105 kPa hydrogel islands leading to larger, polygonal cell shapes. In a parallel effort, a finite element model was constructed to characterize and confirm experimental findings and aid as a predictive tool in modeling cell microenvironments. Signaling pathway inhibition studies suggested that RhoA is a key regulator of cell response to the cooperative effect of the tunable substrate variables. These results are significant for the engineering of cell-extra cellular matrix interfaces and ultimately decoupling matrix bound cues presented to cells in a tissue microenvironment for regenerative medicine.http://europepmc.org/articles/PMC3839898?pdf=render
spellingShingle Greg M Harris
Tarek Shazly
Ehsan Jabbarzadeh
Deciphering the combinatorial roles of geometric, mechanical, and adhesion cues in regulation of cell spreading.
PLoS ONE
title Deciphering the combinatorial roles of geometric, mechanical, and adhesion cues in regulation of cell spreading.
title_full Deciphering the combinatorial roles of geometric, mechanical, and adhesion cues in regulation of cell spreading.
title_fullStr Deciphering the combinatorial roles of geometric, mechanical, and adhesion cues in regulation of cell spreading.
title_full_unstemmed Deciphering the combinatorial roles of geometric, mechanical, and adhesion cues in regulation of cell spreading.
title_short Deciphering the combinatorial roles of geometric, mechanical, and adhesion cues in regulation of cell spreading.
title_sort deciphering the combinatorial roles of geometric mechanical and adhesion cues in regulation of cell spreading
url http://europepmc.org/articles/PMC3839898?pdf=render
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