title: Interplay of Matrix Stiffness and Cell-Cell Contact in Regulating Differentiation of Stem Cells.
abstract: Stem cells are capable of sensing and responding to the mechanical properties of extracellular matrixes (ECMs). It is well-known that, while osteogenesis is promoted on the stiff matrixes, adipogenesis is enhanced on the soft ones. Herein, we report an "abnormal" tendency of matrix-stiffness-directed stem cell differentiation. Well-defined nanoarrays of cell-adhesive arginine-glycine-aspartate (RGD) peptides were modified onto the surfaces of persistently nonfouling poly(ethylene glycol) (PEG) hydrogels to achieve controlled specific cell adhesion and simultaneously eliminate nonspecific protein adsorption. Mesenchymal stem cells were cultivated on the RGD-nanopatterned PEG hydrogels with the same RGD nanospacing but different hydrogel stiffnesses and incubated in the induction medium to examine the effect of matrix stiffness on osteogenic and adipogenic differentiation extents. When stem cells were kept at a low density during the induction period, the differentiation tendency was consistent with the previous reports in the literature; however, both lineage commitments were favored on the stiff matrices at a high cell density. We interpreted such a complicated stiffness effect at a high cell density in two-dimensional culture as the interplay of matrix stiffness and cell-cell contact. As a result, this study strengthens the essence of the stiffness effect and highlights the combinatory effects of ECM cues and cell cues on stem cell differentiation.
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: 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: 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: D002448:Cell Adhesion; D002454:Cell Differentiation; D002478:Cells, Cultured; D005109:Extracellular Matrix; D006801:Humans; D020100:Hydrogels; D059630:Mesenchymal Stem Cells; D010012:Osteogenesis
chemical_list: D020100:Hydrogels
keywords: PEG hydrogel; RGD nanopattern; cell density; cell−cell contact; matrix stiffness; stem cell differentiation