title: Substrate Stiffness Combined with Hepatocyte Growth Factor Modulates Endothelial Cell Behavior.
abstract: Endothelial cells (ECs) play a crucial role in regulating various physiological and pathological processes. The behavior of ECs is modulated by physical (e.g., substrate stiffness) and biochemical cues (e.g., growth factors). However, the synergistic influence of these cues on EC behavior has rarely been investigated. In this study, we constructed poly(l-lysine)/hyaluronan (PLL/HA) multilayer films with different stiffness and exposed ECs to these substrates with and without hepatocyte growth factor (HGF)-supplemented culture medium. We demonstrated that EC adhesion, migration, and proliferation were positively correlated with substrate stiffness and that these behaviors were further promoted by HGF. Interestingly, ECs on the lower stiffness substrates showed stronger responses to HGF in terms of migration and proliferation, suggesting that HGF can profoundly influence stiffness-dependent EC behavior correlated with EC growth. After the formation of an EC monolayer, EC behaviors correlated with endothelial function were evaluated by characterizing monolayer integrity, nitric oxide production, and gene expression of endothelial nitric oxide synthase. For the first time, we demonstrated that endothelial function displayed a negative correlation with substrate stiffness. Although HGF improved endothelial function, HGF was not able to change the stiffness-dependent manner of endothelial functions. Taken together, this study provides insights into the synergetic influence of physical and biochemical cues on EC behavior and offers great potential in the development of optimized biomaterials for EC-based regenerative medicine.
authors.affiliation: MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University , Hangzhou 310027, People's Republic of China.
authors.forename: Hao
authors.initials: H
authors.lastname: Chang
authors.affiliation: CNRS UMR 5628 (LMGP) , 3 parvis Louis Néel, 38016 Grenoble, France.|Université Grenoble Alpes, LMGP , 3 parvis Louis Néel, 38016 Grenoble, France.
authors.forename: Xi-Qiu
authors.initials: XQ
authors.lastname: Liu
authors.affiliation: MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University , Hangzhou 310027, People's Republic of China.
authors.forename: Mi
authors.initials: M
authors.lastname: Hu
authors.affiliation: MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University , Hangzhou 310027, People's Republic of China.
authors.forename: He
authors.initials: H
authors.lastname: Zhang
authors.affiliation: MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University , Hangzhou 310027, People's Republic of China.
authors.forename: Bo-Chao
authors.initials: BC
authors.lastname: Li
authors.affiliation: MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University , Hangzhou 310027, People's Republic of China.
authors.forename: Ke-Feng
authors.initials: KF
authors.lastname: Ren
authors.affiliation: CNRS UMR 5628 (LMGP) , 3 parvis Louis Néel, 38016 Grenoble, France.|Université Grenoble Alpes, LMGP , 3 parvis Louis Néel, 38016 Grenoble, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Boudou
authors.affiliation: INSERM U823, ERL CNRS3148, Université Joseph Fourier, Institut Albert Bonniot , Site Santé, BP170, 38042 Grenoble Cedex 9, France.
authors.forename: Corinne
authors.initials: C
authors.lastname: Albiges-Rizo
authors.affiliation: CNRS UMR 5628 (LMGP) , 3 parvis Louis Néel, 38016 Grenoble, France.|Université Grenoble Alpes, LMGP , 3 parvis Louis Néel, 38016 Grenoble, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Picart
authors.affiliation: MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University , Hangzhou 310027, People's Republic of China.
authors.forename: Jian
authors.initials: J
authors.lastname: Ji
mesh_terms: D002448:Cell Adhesion / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006244:Hardness; D017228:Hepatocyte Growth Factor / Q000494:pharmacology*; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry*; D011107:Polylysine / Q000737:chemistry*; D013499:Surface Properties
chemical_list: D011107:Polylysine; D017228:Hepatocyte Growth Factor; D006820:Hyaluronic Acid