title: Matrix Stiffness and Nanoscale Spatial Organization of Cell-Adhesive Ligands Direct Stem Cell Fate.
abstract: One of the breakthroughs in biomaterials and regenerative medicine in the latest decade is the finding that matrix stiffness affords a crucial physical cue of stem cell differentiation. This statement was recently challenged by another understanding that protein tethering on material surfaces instead of matrix stiffness was the essential cue to regulate stem cells. Herein, we employed nonfouling poly(ethylene glycol) (PEG) hydrogels as the matrix to prevent nonspecific protein adsorption, and meanwhile covalently bound cell-adhesive arginine-glycine-aspartate (RGD) peptides onto the hydrogel surfaces in the form of well-defined nanoarrays to control specific cell adhesion. This approach enables the decoupling of the effects of matrix stiffness and surface chemistry. Mesenchymal stem cells (MSCs) were cultured on four substrates (two compressive moduli of the PEG hydrogels multiplied by two RGD nanospacings) and incubated in the mixed osteogenic and adipogenic medium. The results illustrate unambiguously that matrix stiffness is a potent regulator of stem cell differentiation. Moreover, we reveal that RGD nanospacing affects spreading area and differentiation of rat MSCs, regardless of the hydrogel stiffness. Therefore, both matrix stiffness and nanoscale spatial organization of cell-adhesive ligands direct stem cell fate.
authors.affiliation: State Key Laboratory of Molecular Engineering of Polymers, Collaborative Innovation Center of Polymers and Polymer Composite Materials, Department of Macromolecular Science, Advanced Materials Laboratory, Fudan University, Shanghai 200433, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Ye
authors.affiliation: State Key Laboratory of Molecular Engineering of Polymers, Collaborative Innovation Center of Polymers and Polymer Composite Materials, Department of Macromolecular Science, Advanced Materials Laboratory, Fudan University, Shanghai 200433, China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Molecular Engineering of Polymers, Collaborative Innovation Center of Polymers and Polymer Composite Materials, Department of Macromolecular Science, Advanced Materials Laboratory, Fudan University, Shanghai 200433, China.
authors.forename: Luping
authors.initials: L
authors.lastname: Cao
authors.affiliation: State Key Laboratory of Molecular Engineering of Polymers, Collaborative Innovation Center of Polymers and Polymer Composite Materials, Department of Macromolecular Science, Advanced Materials Laboratory, Fudan University, Shanghai 200433, China.
authors.forename: Shiyu
authors.initials: S
authors.lastname: Li
authors.affiliation: State Key Laboratory of Molecular Engineering of Polymers, Collaborative Innovation Center of Polymers and Polymer Composite Materials, Department of Macromolecular Science, Advanced Materials Laboratory, Fudan University, Shanghai 200433, China.
authors.forename: Zhenhua
authors.initials: Z
authors.lastname: Li
authors.affiliation: State Key Laboratory of Molecular Engineering of Polymers, Collaborative Innovation Center of Polymers and Polymer Composite Materials, Department of Macromolecular Science, Advanced Materials Laboratory, Fudan University, Shanghai 200433, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Yu
authors.affiliation: State Key Laboratory of Molecular Engineering of Polymers, Collaborative Innovation Center of Polymers and Polymer Composite Materials, Department of Macromolecular Science, Advanced Materials Laboratory, Fudan University, Shanghai 200433, China.
authors.forename: Jiandong
authors.initials: J
authors.lastname: Ding
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry*; D002448:Cell Adhesion; D002454:Cell Differentiation; D002478:Cells, Cultured; D019245:Compressive Strength; D020100:Hydrogels / Q000737:chemistry*; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D049329:Nanostructures / Q000737:chemistry; D009842:Oligopeptides / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D051381:Rats
chemical_list: D001672:Biocompatible Materials; D020100:Hydrogels; D009842:Oligopeptides; D011092:Polyethylene Glycols; C047981:arginyl-glycyl-aspartic acid
keywords: Matrix stiffness; RGD nanospacing; cell adhesion; nanopattern; poly(ethylene glycol) (PEG) hydrogel; stem cell differentiation