High-Throughput Discovery of Synthetic Surfaces That Support Proliferation of Pluripotent Cells
Open accessAbstract
Synthetic materials that promote the growth or differentiation of cells have advanced the fields of tissue engineering and regenerative medicine. Most functional biomaterials are based on a handful of peptide sequences derived from protein ligands for cell surface receptors. Because few proteins possess short peptide sequences that alone can engage cell surface receptors, the repertoire of receptors that can be targeted with this approach is limited. Materials that bind diverse classes of receptors, however, may be needed to guide cell growth and differentiation. To provide access to such new materials, we utilized phage display to identify novel peptides that bind to the surface of pluripotent cells. Using human embryonal carcinoma (EC) cells as bait, approximately 3 x 10(4) potential cell-binding phage clones were isolated. The pool was narrowed using an enzyme-linked immunoassay: 370 clones were tested, and seven cell-binding peptides were identified. Of these, six sequences possess EC cell-binding ability. Specifically, when displayed by self-assembled monolayers (SAMs) of alkanethiols on gold, they mediate cell adhesion. The corresponding soluble peptides block this adhesion, indicating that the identified peptide sequences are specific. They also are functional. Synthetic surfaces displaying phage-derived peptides support growth of undifferentiated human embryonic stem (ES) cells. When these cells were cultured on SAMs presenting the sequence TVKHRPDALHPQ or LTTAPKLPKVTR in a chemically defined medium (mTeSR), they expressed markers of pluripotency at levels similar to those of cells cultured on Matrigel. Our results indicate that this screening strategy is a productive avenue for the generation of materials that control the growth and differentiation of cells.
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Stem cell maturation, differentiation, and derived cell function depend critically on temporal and spatial engagement of cell surface integrins with ECM in development and ex vivo culture.
“There is now clear evidence from our group and the work of others that stem cell maturation and differentiation and the proper function of cells derived thereof are critically dependent on the temporal and spatial engagement of cell surface integrins with extracellular matrices (ECM) both in a given organ system during development19 and in the context of ex vivo stem cell culture20–27.”
From In situ expansion, differentiation, and electromechanical coupling of human cardiac muscle in a 3D bioprinted, chambered organoid (2020) · cites this paper as [25]
The Introduction (page unavailable) says extracellular substrates, including ECM, can guide ex vivo stem-cell growth and differentiation. The Results and Discussion (page unavailable) show that integrins largely mediate human ES-cell adhesion to ECM-coated surfaces. The paper does not establish that temporal and spatial integrin–ECM engagement is critical for maturation, differentiation, or derived-cell function; it also reports undifferentiated growth on surfaces that do not act through integrins. (LLM, conf=0.86)
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- Authors
- Derda, R., Musah, S., Orner, B. P., Klim, J. R., Li, L., & Kiessling, L. L.
- Affiliations
- University of Wisconsin–Madison (US)
- University of Wisconsin System (US)
- Corresponding author
- Kiessling, Laura L.
- Venue
- Journal of the American Chemical Society
- Publisher
- American Chemical Society (ACS)
- Published
- 2010-02-03
- Volume
- 132
- Issue
- 4
- Pages
- 1289-1295
- ISSN
- 0002-7863 (ISSN-L)
- 1520-5126
- PMC
- PMC2819098
- OpenAlex
- W2006508505
- Cited by
- 144
- References
- 1
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 1 · 2023: 3 · 2022: 1 · 2021: 4 · 2020: 8 · 2019: 4 · 2018: 8 · 2017: 8 · 2016: 8 · 2015: 10 · 2014: 12 · 2013: 19 · 2012: 19
- FWCI
- 11.21
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of the American Chemical Society (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Research Portal (King's College London) (submittedVersion)
- Funders
- National Science Foundation (0520527)
- W. M. Keck Foundation
- University of Wisconsin-Madison
- National Institutes of Health
- National Institute on Aging (AG19550, F32AG019550)
- National Institute of General Medical Sciences (T32GM008505)
- National Institute of Allergy and Infectious Diseases (R01AI055258, AI055258)
- Division of Materials Research (DMR-0520527)
- Topics
- Physical Sciences › Materials Science › Surfaces, Coatings and Films › Polymer Surface Interaction Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
- Keywords
- cell-binding peptides, phage display, human embryonic stem cells, pluripotency, cell adhesion, self-assembled monolayers, alkanethiol monolayers, gold surfaces, synthetic biomaterials, cell surface receptors, peptide screening
- MeSH terms
- Amino Acid Sequence, Cell Adhesion, Humans, Peptides, Protein Binding, Surface Properties, Peptide Library, Cell Proliferation, Embryonal Carcinoma Stem Cells, Tissue Scaffolds
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