Rewiring cell adhesion.
The adhesion of cells is mediated by the binding of several cell-surface receptors to ligands found in the extracellular matrix. These receptors often have overlapping specificities for the peptide ligands, making it difficult to understand the roles for discrete receptors in cell adhesion, migration, and differentiation as well as to direct the selective adhesion of cell types in tissue-engineering applications. To overcome these limitations, we developed a strategy to rewire the receptor-ligand interactions between a cell and substrate to ensure that adhesion is mediated by a single receptor with unique specificity. The strategy combines a genetic approach to engineer the cell surface with a chimeric integrin receptor having a unique ligand binding domain with a surface chemistry approach to prepare substrates that present ligands that are bound by the new binding domain. We show that Chinese hamster ovary cells that are engineered with a chimeric beta1 integrin adhere, signal, and even migrate on a synthetic matrix.
Kato
Mihoko
M
Department of Chemistry and Institute of Biophysical Dynamics, The University of Chicago, 5735 South Ellis Avenue, Chicago, Illinois 60637, USA.
Mrksich
Milan
M
D000818:Animals; D016466:CHO Cells; D030741:Carbonic Anhydrase IV / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D002257:Carbonic Anhydrase Inhibitors / Q000737:chemistry / Q000494:pharmacology; D002448:Cell Adhesion / Q000502:physiology*; D002465:Cell Movement; D020740:Chimerin Proteins / Q000737:chemistry / Q000235:genetics; D006224:Cricetinae; D051416:Focal Adhesion Protein-Tyrosine Kinases; D039081:Integrin alpha5beta1 / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D009842:Oligopeptides / Q000737:chemistry / Q000378:metabolism; D010766:Phosphorylation; D015202:Protein Engineering / Q000379:methods; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D013449:Sulfonamides / Q000737:chemistry / Q000494:pharmacology; D013499:Surface Properties; D014162:Transfection; D000096926:Benzenesulfonamides
D030741:Carbonic Anhydrase IV; D002257:Carbonic Anhydrase Inhibitors; D020740:Chimerin Proteins; D051416:Focal Adhesion Protein-Tyrosine Kinases; D039081:Integrin alpha5beta1; D009842:Oligopeptides; D011505:Protein-Tyrosine Kinases; D013449:Sulfonamides; D000096926:Benzenesulfonamides