title: Deciphering the combinatorial roles of geometric, mechanical, and adhesion cues in regulation of cell spreading.
abstract: 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.
authors.affiliation: Department of Chemical Engineering, University of South Carolina, Columbia, South Carolina, United States of America.
authors.forename: Greg M
authors.initials: GM
authors.lastname: Harris
authors.forename: Tarek
authors.initials: T
authors.lastname: Shazly
authors.forename: Ehsan
authors.initials: E
authors.lastname: Jabbarzadeh
mesh_terms: D002448:Cell Adhesion; D002465:Cell Movement; D002478:Cells, Cultured; D004548:Elasticity; D005109:Extracellular Matrix; D020342:Finite Element Analysis; D005455:Fluorescent Antibody Technique; D006801:Humans; D020100:Hydrogels; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000201:enzymology; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors
chemical_list: D020100:Hydrogels; D054460:rho-Associated Kinases