title: Self-Assembly and Collagen-Stimulating Activity of a Peptide Amphiphile Incorporating a Peptide Sequence from Lumican.
abstract: The self-assembly and bioactivity of a peptide amphiphile (PA) incorporating a 13-residue sequence derived from the last 13 amino acids of the C-terminus of lumican, C16-YEALRVANEVTLN, attached to a hexadecyl (C16) lipid chain have been examined. Lumican is a proteoglycan found in many types of tissue and is involved in collagen fibril organization. A critical aggregation concentration (cac) for the PA was determined through pyrene fluorescence measurements. The structure of the aggregates was imaged using electron microscopy, and twisted and curved nanotapes were observed. In situ small-angle X-ray scattering and fiber X-ray diffraction reveal that these tapes contain interdigitated bilayers of the PA molecules. FTIR and circular dichroism spectroscopy and fiber X-ray diffraction indicate that the lumican sequence in the PA adopts a β-sheet secondary structure. Cell assays using human dermal fibroblasts show that below the cac the PA displays good biocompatibility and also stimulates collagen production over a period of 3 weeks, exceeding a 2-fold enhancement for several concentrations. Thus, this PA has promise in future biological applications, in particular, in tissue engineering.
authors.affiliation: †School of Chemistry, Pharmacy and Food Biosciences, University of Reading, Whiteknights, Reading RG6 6AD, United Kingdom.
authors.forename: Ian W
authors.initials: IW
authors.lastname: Hamley
authors.affiliation: †School of Chemistry, Pharmacy and Food Biosciences, University of Reading, Whiteknights, Reading RG6 6AD, United Kingdom.
authors.forename: Ashkan
authors.initials: A
authors.lastname: Dehsorkhi
authors.affiliation: †School of Chemistry, Pharmacy and Food Biosciences, University of Reading, Whiteknights, Reading RG6 6AD, United Kingdom.
authors.forename: Valeria
authors.initials: V
authors.lastname: Castelletto
authors.affiliation: ‡Institute of Genetic Medicine, Newcastle University, International Centre for Life, Central Parkway, Newcastle upon Tyne NE1 3BZ, United Kingdom.
authors.forename: Merlin N M
authors.initials: MN
authors.lastname: Walter
authors.affiliation: ‡Institute of Genetic Medicine, Newcastle University, International Centre for Life, Central Parkway, Newcastle upon Tyne NE1 3BZ, United Kingdom.
authors.forename: Che J
authors.initials: CJ
authors.lastname: Connon
authors.affiliation: §Department of Applied Physics, Aalto University School of Science, P.O. Box 15100, FI-00076 Aalto, Finland.
authors.forename: Mehedi
authors.initials: M
authors.lastname: Reza
authors.affiliation: §Department of Applied Physics, Aalto University School of Science, P.O. Box 15100, FI-00076 Aalto, Finland.
authors.forename: Janne
authors.initials: J
authors.lastname: Ruokolainen
mesh_terms: D000595:Amino Acid Sequence; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D011508:Chondroitin Sulfate Proteoglycans / Q000737:chemistry*; D003094:Collagen / Q000819:agonists* / Q000096:biosynthesis; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005456:Fluorescent Dyes; D006801:Humans; D007632:Keratan Sulfate / Q000737:chemistry*; D000071234:Lumican; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis / Q000494:pharmacology*; D017433:Protein Structure, Secondary; D011721:Pyrenes
chemical_list: D011508:Chondroitin Sulfate Proteoglycans; D005456:Fluorescent Dyes; C000604306:LUM protein, human; D000071234:Lumican; D010455:Peptides; D011721:Pyrenes; D003094:Collagen; D007632:Keratan Sulfate; C030984:pyrene