title: The molecular mechanism of mediation of adsorbed serum proteins to endothelial cells adhesion and growth on biomaterials.
abstract: To explore molecular mechanism of mediation of adsorbed proteins to cell adhesion and growth on biomaterials, this study examined endothelial cell adhesion, morphology and viability on bare and titanium nitride (TiN) coated nickel titanium (NiTi) alloys and chitosan film firstly, and then identified the type and amount of serum proteins adsorbed on the three surfaces by proteomic technology. Subsequently, the mediation role of the identified proteins to cell adhesion and growth was investigated with bioinformatics analyses, and further confirmed by a series of cellular and molecular biological experiments. Results showed that the type and amount of adsorbed serum proteins associated with cell adhesion and growth was obviously higher on the alloys than on the chitosan film, and these proteins mediated endothelial cell adhesion and growth on the alloys via four ways. First, proteins such as adiponectin in the adsorbed protein layer bound with cell surface receptors to generate signal transduction, which activated cell surface integrins through increasing intracellular calcium level. Another way, thrombospondin 1 in the adsorbed protein layer promoted TGF-β signaling pathway activation and enhanced integrins expression. The third, RGD sequence containing proteins such as fibronectin 1, vitronectin and thrombospondin 1 in the adsorbed protein layer bound with activated integrins to activate focal adhesion pathway, increased focal adhesion formation and actin cytoskeleton organization and mediated cell adhesion and spreading. In addition, the activated focal adhesion pathway promoted the expression of cell growth related genes and resulted in cell proliferation. The fourth route, coagulation factor II (F2) and fibronectin 1 in the adsorbed protein layer bound with cell surface F2 receptor and integrin, activated regulation of actin cytoskeleton pathway and regulated actin cytoskeleton organization.
authors: State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096, PR China.
authors: Dayun
authors: D
authors: Yang
authors: Xiaoying
authors: X
authors: Lü
authors: Ying
authors: Y
authors: Hong
authors: Tingfei
authors: T
authors: Xi
authors: Deyuan
authors: D
authors: Zhang
mesh_terms: D008841:Actin Cytoskeleton / Q000187:drug effects / Q000378:metabolism; D000327:Adsorption / Q000187:drug effects; D000497:Alloys / Q000494:pharmacology; D001672:Biocompatible Materials / Q000378:metabolism* / Q000494:pharmacology; D001798:Blood Proteins / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D048271:Chitosan / Q000494:pharmacology; D020099:Coated Materials, Biocompatible / Q000494:pharmacology; D019295:Computational Biology; D042783:Endothelial Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D022001:Focal Adhesions / Q000187:drug effects / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D008024:Ligands; D018625:Microscopy, Atomic Force; D009842:Oligopeptides / Q000494:pharmacology; D040901:Proteomics; D015203:Reproducibility of Results; D013499:Surface Properties; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D000497:Alloys; D001672:Biocompatible Materials; D001798:Blood Proteins; D020099:Coated Materials, Biocompatible; D008024:Ligands; D009842:Oligopeptides; D016212:Transforming Growth Factor beta; C047981:arginyl-glycyl-aspartic acid; D048271:Chitosan; D002118:Calcium