High-Throughput Discovery of Targeted, Minimally Complex Peptide Surfaces for Human Pluripotent Stem Cell Culture
| Autor: | Caroline Sugnaux, Riya Muckom, Barbara L. Ekerdt, Anusuya Ramasubramanian, Kevin E. Healy, David V. Schaffer, Douglas S. Clark, Christina M. Fuentes |
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| Rok vydání: | 2021 |
| Předmět: |
Pluripotent Stem Cells
biology Chemistry 0206 medical engineering Biomedical Engineering Regulator 02 engineering and technology Computational biology 021001 nanoscience & nanotechnology 020601 biomedical engineering Regenerative medicine Biomaterials Laminin biology.protein Humans Stem cell Signal transduction Cell Self Renewal 0210 nano-technology Receptor Panning (camera) Induced pluripotent stem cell Peptides Cell Proliferation |
| Zdroj: | ACS biomaterials scienceengineering. 7(4) |
| ISSN: | 2373-9878 |
| Popis: | Human pluripotent stem cells harbor an unlimited capacity to generate therapeutically relevant cells for applications in regenerative medicine. However, to utilize these cells in the clinic, scalable culture systems that activate defined receptors and signaling pathways to sustain stem cell self-renewal are required; and synthetic materials offer considerable promise to meet these needs. De novo development of materials that target novel pathways has been stymied by a limited understanding of critical receptor interactions maintaining pluripotency. Here, we identify peptide agonists for the human pluripotent stem cell (hPSC) laminin receptor and pluripotency regulator, α6-integrin, through unbiased, library-based panning strategies. Biophysical characterization of adhesion suggests that identified peptides bind hPSCs through α6-integrin with sub-μM dissociation constants similar to laminin. By harnessing a high-throughput microculture platform, we developed predictive guidelines for presenting these integrin-targeting peptides alongside canonical binding motifs at optimal stoichiometries to generate nascent culture surfaces. Finally, when presented as self-assembled monolayers, predicted peptide combinations supported hPSC expansion, highlighting how unbiased screens can accelerate the discovery of targeted biomaterials. |
| Databáze: | OpenAIRE |
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