In vitro assessment of the cytotoxic effects of novel RGD analogues

Balacheva, Anelia; Илиев, Иван; Detcheva, Roumyana; Dzimbova, Tatyana; Pajpanova, Tamara; Golovinsky, Evgeny

doi:10.7750/biodiscovery.2012.4.1

Cited by 1 publication

(3 citation statements)

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“…It is not uncommon to observe multiple responses for the same compound between different cell lines, be it related to metabolic activity, cytotoxicity, proliferation, or cell adhesion. This effect was also observed previously in other RGDS-based molecules, with different levels of cell adhesion and cytotoxicity for the same molecule for distinct cell types. ,, …”

Section: Discussionsupporting

confidence: 85%

Section: Discussionmentioning

confidence: 99%

“…This effect was also observed previously in other RGDS-based molecules, with different levels of cell adhesion and cytotoxicity for the same molecule for distinct cell types. 34,131,132 A possible explanation for the increased cytotoxicity in fibroblasts is the fact that soluble RGD-peptides may trigger apoptosis by the inhibition of vitronectin and fibronectin domains, promoting cell detachment and leading to anoikis, a type of programmed cell death that occurs in anchoragedependent cells upon detachment from the surrounding extracellular matrix or substrate, an effect that has already been observed for fibroblasts. 32,133,134 The observation of fibril textures for the lipopeptides (which in several cases show spontaneous flow alignment) is particularly interesting in terms of further research underway on the preparation of aligned scaffolds for tissue engineering 135 using the alignment of myoblasts to improve the texture of cultured meat.…”

Section: ■ Conclusionmentioning

confidence: 99%

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Cell Adhesion Motif-Functionalized Lipopeptides: Nanostructure and Selective Myoblast Cytocompatibility

et al. 2022

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The conformation and self-assembly of four lipopeptides, peptide amphiphiles comprising peptides conjugated to lipid chains, in aqueous solution have been examined. The peptide sequence in all four lipopeptides contains the integrin cell adhesion RGDS motif, and the cytocompatibility of the lipopeptides is also analyzed. Lipopeptides have either tetradecyl (C 14 , myristyl) or hexadecyl (C 16 , palmitoyl) lipid chains and peptide sequence WGGRGDS or GGGRGDS, that is, with either a tryptophan-containing WGG or triglycine GGG tripeptide spacer between the bioactive peptide motif and the alkyl chain. All four lipopeptides self-assemble above a critical aggregation concentration (CAC), determined through several comparative methods using circular dichroism (CD) and fluorescence. Spectroscopic methods [CD and Fourier transform infrared (FTIR) spectroscopy] show the presence of β-sheet structures, consistent with the extended nanotape, helical ribbon, and nanotube structures observed by cryogenic transmission electron microscopy (cryo-TEM). The high-quality cryo-TEM images clearly show the coexistence of helically twisted ribbon and nanotube structures for C 14 -WGGRGDS, which highlight the mechanism of nanotube formation by the closure of the ribbons. Small-angle X-ray scattering shows that the nanotapes comprise highly interdigitated peptide bilayers, which are also present in the walls of the nanotubes. Hydrogel formation was observed at sufficiently high concentrations or could be induced by a heat/cool protocol at lower concentrations. Birefringence due to nematic phase formation was observed for several of the lipopeptides, along with spontaneous flow alignment of the lyotropic liquid crystal structure in capillaries. Cell viability assays were performed using both L929 fibroblasts and C2C12 myoblasts to examine the potential uses of the lipopeptides in tissue engineering, with a specific focus on application to cultured (lab-grown) meat, based on myoblast cytocompatibility. Indeed, significantly higher cytocompatibility of myoblasts was observed for all four lipopeptides compared to that for fibroblasts, in particular at a lipopeptide concentration below the CAC. Cytocompatibility could also be improved using hydrogels as cell supports for fibroblasts or myoblasts. Our work highlights that precision control of peptide sequences using bulky aromatic residues within "linker sequences" along with alkyl chain selection can be used to tune the self-assembled nanostructure. In addition, the RGDS-based lipopeptides show promise as materials for tissue engineering, especially those of muscle precursor cells.

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Section: Discussionsupporting

confidence: 85%

Section: Discussionmentioning

confidence: 99%