Collagen-stimulating activity of a pentapeptide conjugate and self-assembly into micelles

We present a lipopeptide conjugate, farnesyl-mercapto(diethylene glycol)-KTTKS (FMdEG-KTTKS), designed to include the KTTKS collagen-stimulating sequence attached to a terpenoid branched lipid chain via a short hydrophilic spacer. This conjugate stimulates fibroblasts to produce greater than 200% more collagen per cell than conventional stimulants. This activity is observed at low concentration, well below a critical micelle concentration (CMC) determined by fluorescence probe measurements. Above the CMC, this molecule self-assembles into well-defined spherical micelles, as shown by cryogenic-transmission electron microscopy (cryo-TEM) and small-angle X-ray scattering (SAXS). The behaviour of this conjugate is contrasted with that of related lipopeptides: FMdEG-KTTKS forms micelles across a wide pH range, instead of nanotapes observed for C₁₆-KTTKS (Matrixyl™). The molecule is shown to stimulate production of type I collagen (beneficial for anti-aging treatments) and promotes repopulation of fibroblasts in a cell monolayer after scratching, as a simple model for skin injury. FMdEG-KTTKS also has anti-inflammatory activity, reducing the production of nitrite in macrophages challenged with bacterial lipopolysaccharide.