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

Abstract

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.

Novel temperature-responsive polymer brushes with carbohydrate residues facilitate selective adhesion and collection of hepatocytes

“…Although the versatility of the RGD peptide is attractive for surface modification, the use of highly specific sequences with strong affinities toward particular types of cell has gained much attention in the area of cell isolation [19]. An important risk in the clinical application of induced pluripotent stem (iPS) cells, for example, is residual undifferentiated cells that can induce spontaneous tumorigenesis in vivo [20].…”

Strategies and Techniques to Enhance theIn SituEndothelialization of Small-Diameter Biodegradable Polymeric Vascular Grafts

“…79 CAG peptide was shown to selectively enhance attachment of ECs while rejecting SMC adhesion. 80 CAG was mixed with PCL and electrospun into fibers used to form a graft with an inner diameter of 0.7 mm. The area of endothelialization of the CAG-PCL grafts compared with PCL grafts was higher at 1, 2, and 6 weeks after implantation.…”

Combinational Effects of Polymer Viscoelasticity and Immobilized Peptides on Cell Adhesion to Cell-selective Scaffolds

“…1,2 To enhance cell adhesion performance for higher bio-compatibility, scaffolds have been coated with biomolecules such as muscle cell (SMC) adhesion. [9][10][11] In our study, apart from ECMderived short peptides for cell-selective peptides, we found that several simple peptide sequences also show cell-selective adhesion performances. For example, Ile-repeating peptides show clear EC-selective adhesion capacity, 12 and various "analog sequences" have shown similar performances.…”

“…The EC-selective adhesion peptide, CAG, was originally obtained from a peptide array screening, and was applied to the PCL polymer resulting in the enhancement of EC-selective adhesion in vitro and vivo. [9][10][11] However, among our scaffolds in this work, the CAG provided its EC-selective adhesion performance on P2, P4, and P6. By the fold-change, P2 enhanced EC-adhesion 1.7-fold higher than FB-adhesion, P4 and P6 enhanced EC-adhesion higher than both FB-and SMC-adhesion (>2.0-fold).…”

“…CAG and III, both screened as EC-selective peptides, 9,12 indicated that the effects of ECselective adhesion could be increased on CAG-immobilized P2/P4 (FB versus EC versus SMC: p < 0.05). RRR, screened as an FB-selective peptide, 12 indicated that the effects of FBselective adhesion could be enhanced by combination with P6 (FB versus EC versus SMC: p <0.05).…”