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Suppression of cell adhesion through specific integrin crosstalk on mixed peptide-polysaccharide matrices
Affiliation:1. Tianjin Key Laboratory of Applied Catalysis Science and Technology, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300354, China;2. Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin 300072, China;3. Tianjin Engineering Research Center of Functional Fine Chemicals, Tianjin 300354, China
Abstract:Crosstalk of different integrins, which bind to distinct types of extracellular matrix proteins, promotes specific functions. This crosstalk has not been investigated in depth. Previously, we demonstrated that integrin-syndecan crosstalk accelerated cell adhesion. Here, we evaluated the crosstalk of two different integrins using mixed peptide-polysaccharide (chitosan or alginate) matrices. Two different integrin binding peptides, FIB1 (integrin αvβ3), EF1zz (integrin α2β1), and 531 (integrin α3β1), were mixed in various molar ratios (9:1, 4:1, 1:1) and conjugated on a polysaccharide matrix. The mixture of FIB1/EF1zz- and FIB1/531-polysaccharide matrices did not show any difference in human dermal fibroblast (HDF) adhesion against the mono polysaccharide matrices. Interestingly, the EF1zz/531-polysaccharide matrix (molar ratio = 1:4) exhibited significantly decreased cell adhesion, but other EF1zz/531-polysaccharide matrices did not show any difference. When we examined the signal transduction of the EF1zz/531(1:4), Y397 phosphorylation of FAK significantly decreased but Y514 phosphorylation of Src did not exhibit any differences. Further investigation revealed that this suppression was mediated by PI3K signaling through the activation of integrin, and PKA signaling modulated suppression of HDF attachment. These findings suggest that a mixed peptide-polysaccharide matrix using receptor specific ligands can regulate cellular functions through receptor-specific crosstalk and is a useful approach to understand receptor specific crosstalk.
Keywords:Cell adhesion  Crosstalk  Integrin  Peptide  Polysaccharide  ECM (extracellular matrix)  ECM"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  kwrd0045"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  extracellular matrix  Fmoc"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  kwrd0055"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  9-fluorenylmethoxycarbonyl  MBS"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  kwrd0065"  },"  $$"  :[{"  #name"  :"  text"  ,"  $$"  :[{"  #name"  :"  italic"  ,"  _"  :"  N"  },{"  #name"  :"  __text__"  ,"  _"  :"  -("  },{"  #name"  :"  italic"  ,"  _"  :"  m"  },{"  #name"  :"  __text__"  ,"  _"  :"  -maleimidobenzoyloxy) succinimide  DMF"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  kwrd0075"  },"  $$"  :[{"  #name"  :"  text"  ,"  $$"  :[{"  #name"  :"  italic"  ,"  _"  :"  N"  },{"  #name"  :"  __text__"  ,"  _"  :"  ,"  },{"  #name"  :"  italic"  ,"  _"  :"  N"  },{"  #name"  :"  __text__"  ,"  _"  :"  ′-dimethylformamide  DMEM"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  kwrd0085"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  dulbecco's modified essential medium  FBS"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  kwrd0095"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  fetal bovine serum  BSA"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  kwrd0105"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  bovine serum albumin  HDF"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  kwrd0115"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  human dermal fibroblast  FAK"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  kwrd0125"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  focal adhesion kinase
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