title: Self-assembly of a dual functional bioactive peptide amphiphile incorporating both matrix metalloprotease substrate and cell adhesion motifs.
abstract: We describe a bioactive lipopeptide that combines the capacity to promote the adhesion and subsequent self-detachment of live cells, using template-cell-environment feedback interactions. This self-assembling peptide amphiphile comprises a diene-containing hexadecyl lipid chain (C16e) linked to a matrix metalloprotease-cleavable sequence, Thr-Pro-Gly-Pro-Gln-Gly-Ile-Ala-Gly-Gln, and contiguous with a cell-attachment and signalling motif, Arg-Gly-Asp-Ser. Biophysical characterisation revealed that the PA self-assembles into 3 nm diameter spherical micelles above a critical aggregation concentration (cac). In addition, when used in solution at 5-150 nM (well below the cac), the PA is capable of forming film coatings that provide a stable surface for human corneal fibroblasts to attach and grow. Furthermore, these coatings were demonstrated to be sensitive to metalloproteases expressed endogenously by the attached cells, and consequently to elicit the controlled detachment of cells without compromising their viability. As such, this material constitutes a novel class of multi-functional coating for both fundamental and clinical applications in tissue engineering.
authors.affiliation: School of Chemistry, Pharmacy and Food Biosciences, University of Reading, Whiteknights, Reading, RG6 6AD, UK. I.W.Hamley@reading.ac.uk.
authors.forename: Ashkan
authors.initials: A
authors.lastname: Dehsorkhi
authors.forename: Ricardo M
authors.initials: RM
authors.lastname: Gouveia
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Smith
authors.forename: Ian W
authors.initials: IW
authors.lastname: Hamley
authors.forename: Valeria
authors.initials: V
authors.lastname: Castelletto
authors.forename: Che J
authors.initials: CJ
authors.lastname: Connon
authors.forename: Mehedi
authors.initials: M
authors.lastname: Reza
authors.forename: Janne
authors.initials: J
authors.lastname: Ruokolainen
mesh_terms: D000595:Amino Acid Sequence; D002448:Cell Adhesion / Q000187:drug effects; D002478:Cells, Cultured; D006801:Humans; D045726:Metalloproteases / Q000378:metabolism*; D008823:Micelles; D009842:Oligopeptides / Q000138:chemical synthesis / Q000494:pharmacology; D010455:Peptides / Q000138:chemical synthesis / Q000378:metabolism* / Q000494:pharmacology; D053838:Scattering, Small Angle; D013379:Substrate Specificity; D013696:Temperature; D014961:X-Ray Diffraction
chemical_list: D008823:Micelles; D009842:Oligopeptides; D010455:Peptides; C046617:arginyl-glycyl-aspartyl-serine; D045726:Metalloproteases