title: Supra-molecular assembly of a lumican-derived peptide amphiphile enhances its collagen-stimulating activity.
abstract: C16-YEALRVANEVTLN, a peptide amphiphile (PA) incorporating a biologically active amino acid sequence found in lumican, has been examined for its influence upon collagen synthesis by human corneal fibroblasts in vitro, and the roles of supra-molecular assembly and activin receptor-like kinase ALK receptor signaling in this effect were assessed. Cell viability was monitored using the Alamar blue assay, and collagen synthesis was assessed using Sirius red. The role of ALK signaling was studied by receptor inhibition. Cultured human corneal fibroblasts synthesized significantly greater amounts of collagen in the presence of the PA over both 7-day and 21-day periods. The aggregation of the PA to form nanotapes resulted in a notable enhancement in this activity, with an approximately two-fold increase in collagen production per cell. This increase was reduced by the addition of an ALK inhibitor. The data presented reveal a stimulatory effect upon collagen synthesis by the primary cells of the corneal stroma, and demonstrate a direct influence of supra-molecular assembly of the PA upon the cellular response observed. The effects of PA upon fibroblasts were dependent upon ALK receptor function. These findings elucidate the role of self-assembled nanostructures in the biological activity of peptide amphiphiles, and support the potential use of a self-assembling lumican derived PA as a novel biomaterial, intended to promote collagen deposition for wound repair and tissue engineering purposes.
authors.affiliation: Institute of Genetic Medicine, International Centre for Life, Newcastle University, Newcastle upon Tyne, NE1 3BZ, UK. che.connon@newcastle.ac.uk.
authors.forename: Merlin N M
authors.initials: MN
authors.lastname: Walter
authors.affiliation: Department of Chemistry, University of Reading, Whiteknights, Reading, RG6 6AD, UK.
authors.forename: Ashkan
authors.initials: A
authors.lastname: Dehsorkhi
authors.affiliation: Department of Chemistry, University of Reading, Whiteknights, Reading, RG6 6AD, UK.
authors.forename: Ian W
authors.initials: IW
authors.lastname: Hamley
authors.affiliation: Institute of Genetic Medicine, International Centre for Life, Newcastle University, Newcastle upon Tyne, NE1 3BZ, UK. che.connon@newcastle.ac.uk.
authors.forename: Che J
authors.initials: CJ
authors.lastname: Connon
mesh_terms: D029404:Activin Receptors / Q000737:chemistry* / Q000378:metabolism; D000595:Amino Acid Sequence; D001672:Biocompatible Materials / Q000737:chemistry* / Q000378:metabolism; D002470:Cell Survival; D003094:Collagen / Q000138:chemical synthesis* / Q000737:chemistry; D003319:Corneal Stroma / Q000737:chemistry* / Q000187:drug effects; D005347:Fibroblasts / Q000737:chemistry* / Q000187:drug effects; D006801:Humans; D000071234:Lumican / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D015398:Signal Transduction; D023822:Tissue Engineering
chemical_list: D001672:Biocompatible Materials; D000071234:Lumican; D010455:Peptides; D003094:Collagen; D029404:Activin Receptors