Spatial control of cell fate using synthetic surfaces to potentiate TGF-β signaling

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 108; no. 29; pp. 11745 - 11750
• Main Authors: Li, Lingyin, Klim, Joseph R., Derda, Ratmir, Courtney, Adam H., Kiessling, Laura L.
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 19.07.2011; National Acad Sciences
• Series: Inaugural Article
• Subjects: Animals; Biological Sciences; Cell adhesion; Cell culture techniques; Cell Differentiation - physiology; Cell growth; Cell Line; Cell Lineage - physiology; Cell lines; Cultured cells; Delta cells; DNA Primers - genetics; Epithelial cells; Flow Cytometry; Fluorescent Antibody Technique; Gene Expression Profiling; Gold; Humans; Ligands; Mesenchymal stem cells; Mice; Microarray Analysis; Peptides - metabolism; Physical Sciences; Receptors; Receptors, Transforming Growth Factor beta - metabolism; Reverse Transcriptase Polymerase Chain Reaction; Signal Transduction - physiology; Stem cells; Surface Properties; Transforming Growth Factor beta - metabolism
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.1101454108

In organisms, cell-fate decisions result from external cues presented by the extracellular microenvironment or the niche. In principle, synthetic niches can be engineered to give rise to patterned cell signaling, an advance that would transform the fields of tissue engineering and regenerative medicine. Biomaterials that display adhesive motifs are critical steps in this direction, but promoting localized signaling remains a major obstacle. We sought to exert precise spatial control over activation of TGF-β signaling. TGF-β signaling, which plays fundamental roles in development, tissue homeostasis, and cancer, is initiated by receptor oligomerization. We therefore hypothesized that preorganizing the transmembrane receptors would potentiate local TGF-β signaling. To generate surfaces that would nucleate the signaling complex, we employed defined self-assembled monolayers that present peptide ligands to TGF-β receptors. These displays of nondiffusible ligands do not compete with the growth factor but rather sensitize bound cells to subpicomolar concentrations of endogenous TGF-β. Cells adhering to the surfaces undergo TGF-β-mediated growth arrest and the epithelial to mesenchymal transition. Gene expression profiles reveal that the surfaces selectively regulate TGF-β responsive genes. This strategy provides access to tailored surfaces that can deliver signals with spatial control.