Mixed peptide-chitosan membranes to mimic the biological activities of a multifunctional laminin alpha1 chain LG4 module

Biomaterials. 2009 Mar;30(8):1596-603. doi: 10.1016/j.biomaterials.2008.12.011. Epub 2009 Jan 4.

Abstract

Laminin alpha1 chain LG4 module is multifunctional and interacts with syndecans and integrin alpha2beta1 via AG73 (RKRLQVQLSIRT) and EF-I (DYATLQLQEGRLHFMFDLG) sites, respectively. Here, we conjugated the AG73 and EF1zz (ATLQLQEGRLHFXFDLGKGR, X: Nle) peptides on a chitosan membrane in various ratios to develop an LG4 mimic biomaterial. The AG73-chitosan membrane promoted strong cell attachment with membrane ruffling and the EF1zz-chitosan membrane promoted integrin-mediated cell adhesion with well-organized actin stress fibers. When AG73 and EF1zz were conjugated on a chitosan membrane with 1:9 molar ratio, the mixed peptide-chitosan membrane promoted the strong cell attachment and neurite outgrowth similar to that on the recombinant LG4 protein. Well-organized actin stress fibers and vinculin accumulated focal contacts were observed in the cells attached on the AG73:EF1zz (molar ratio=1:9)-chitosan membrane. These results suggest that the mixed peptide-chitosan membrane interacts with both syndecans and integrin alpha2beta1 and mimics the cell adhesion of a multifunctional LG4 protein. The mixed peptide-chitosan approach has potential as a multifunctional biomaterial for cell and tissue engineering.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism
  • Animals
  • Cell Adhesion / drug effects
  • Cell Shape / drug effects
  • Cell Size / drug effects
  • Chitosan / pharmacology*
  • Edetic Acid / pharmacology
  • Fibroblasts / cytology
  • Fibroblasts / drug effects
  • Heparin / pharmacology
  • Humans
  • Laminin / chemistry*
  • Laminin / pharmacology*
  • Membranes, Artificial*
  • Mice
  • Molecular Mimicry / drug effects*
  • Neurites / drug effects
  • Neurites / metabolism
  • PC12 Cells
  • Peptide Fragments / pharmacology
  • Peptides / pharmacology*
  • Rats
  • Recombinant Proteins / pharmacology
  • Stress Fibers / drug effects
  • Stress Fibers / metabolism
  • Vinculin / metabolism

Substances

  • AG 73
  • Actins
  • Laminin
  • Membranes, Artificial
  • Peptide Fragments
  • Peptides
  • Recombinant Proteins
  • Vinculin
  • laminin A
  • Heparin
  • Chitosan
  • Edetic Acid