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Collagen type IV-specific tripeptides for selective adhesion of endothelial and smooth muscle cells

Controlling the balance of endothelial cells (ECs) and smooth muscle cells (SMCs) in blood vessels is critically important to minimize the risk associated with vascular implants. Extracellular matrix (ECM) plays a key role in controlling the cellular balance, suggesting a promising source of cell‐se...

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Published in:Biotechnology and bioengineering 2012-07, Vol.109 (7), p.1808-1816
Main Authors: Kanie, Kei, Narita, Yuji, Zhao, Yingzi, Kuwabara, Fumiaki, Satake, Makoto, Honda, Susumu, Kaneko, Hiroaki, Yoshioka, Tomohiko, Okochi, Mina, Honda, Hiroyuki, Kato, Ryuji
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Language:English
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Summary:Controlling the balance of endothelial cells (ECs) and smooth muscle cells (SMCs) in blood vessels is critically important to minimize the risk associated with vascular implants. Extracellular matrix (ECM) plays a key role in controlling the cellular balance, suggesting a promising source of cell‐selective peptides. To obtain EC‐ or SMC‐selective peptides, we start by highlighting sequence differences found among ECM molecules as enriched targets for cell‐selective peptides. We explored the EC‐ or SMC‐selective performance of tripeptides that are specifically enriched only in collagen type IV, but not in types I, II, III, and V. Collagen type IV was chosen since it is the major ECM in the basement membrane of blood vessels, which separates ECs and SMCs. Among 114 collagen type IV‐derived tripeptides pre‐screened from in silico analysis, 22 peptides (19%) were found to promote cell‐selective adhesion, as determined by peptide array. One of the best performing EC‐selective peptides (Cys‐Ala‐Gly (CAG)) was mixed into an electrospun fine‐fiber, a vascular graft material, for practical application. Compared to unmodified fiber, the CAG containing fiber surface was found to enhance adhesion of ECs (+190%) while limiting SMCs (−20%). These results are not only consistent with the hypothesis of ECM as a source of cell selective peptides, but also suggest a new genre of EC‐ or SMC‐selective peptides for tissue engineering applications. Collectively, these findings favorably support the screening approach used to discover new peptides for these purposes. Biotechnol. Bioeng. 2012; 109:1808–1816. © 2012 Wiley Periodicals, Inc. To control the balance of endothelial cells (ECs) and smooth muscle cells (SMCs) (cell‐selectivity) and to minimize the risk with vascular implantation, Kanie and coworkers investigated collagen type IV, the major extracellular matrix (ECM) in the basement membrane (BM), for cell‐selective peptides. With our peptide array‐based screening combined with in silico analysis, peptides with a cell‐selective property were effectively found. One of the EC‐selective peptides provided cell selectivity when introduced to the electrospun fine‐fiber for the vascular graft material.
ISSN:0006-3592
1097-0290
DOI:10.1002/bit.24459