title: Mixed extracellular matrix ligands synergistically modulate integrin adhesion and signaling.
abstract: Cell adhesion to extracellular matrix (ECM) components through cell-surface integrin receptors is essential to the formation, maintenance and repair of numerous tissues, and therefore represents a central theme in the design of bioactive materials that successfully interface with the body. While the adhesive responses associated with a single ligand have been extensively analyzed, the effects of multiple integrin subtypes binding to multivalent ECM signals remain poorly understood. In the present study, we generated a high throughput platform of non-adhesive surfaces presenting well-defined, independent densities of two integrin-specific engineered ligands for the type I collagen (COL-I) receptor alpha(2)beta(1) and the fibronectin (FN) receptor alpha(5)beta(1) to evaluate the effects of integrin cross-talk on adhesive responses. Engineered surfaces displayed ligand density-dependent adhesive effects, and mixed ligand surfaces significantly enhanced cell adhesion strength and focal adhesion assembly compared to single FN and COL-I ligand surfaces. Moreover, surfaces presenting mixed COL-I/FN ligands synergistically enhanced FAK activation compared to the single ligand substrates. The enhanced adhesive activities of the mixed ligand surfaces also promoted elevated proliferation rates. Our results demonstrate interplay between multivalent ECM ligands in adhesive responses and downstream cellular signaling.
authors.affiliation: Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, Georgia, USA.
authors.forename: Catherine D
authors.initials: CD
authors.lastname: Reyes
authors.forename: Timothy A
authors.initials: TA
authors.lastname: Petrie
authors.forename: Andrés J
authors.initials: AJ
authors.lastname: García
mesh_terms: D019921:Biotinylation; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D024042:Collagen Type I / Q000378:metabolism*; D004789:Enzyme Activation; D005353:Fibronectins / Q000378:metabolism*; D005354:Fibrosarcoma / Q000378:metabolism / Q000473:pathology; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism; D022001:Focal Adhesions / Q000378:metabolism; D006801:Humans; D038982:Integrin alpha2beta1 / Q000378:metabolism*; D039081:Integrin alpha5beta1 / Q000378:metabolism*; D008024:Ligands; D010446:Peptide Fragments / Q000378:metabolism*; D020239:Receptor Cross-Talk; D015398:Signal Transduction
chemical_list: D024042:Collagen Type I; D005353:Fibronectins; D038982:Integrin alpha2beta1; D039081:Integrin alpha5beta1; D008024:Ligands; D010446:Peptide Fragments; D051416:Focal Adhesion Protein-Tyrosine Kinases