Cationic Pentapeptide Lipopeptides C16-KTTKS and C16-RTTRS Stimulate Collagen Production in Human Fibroblasts

The integrity of the skin's extracellular matrix, primarily composed of collagen, is crucial for maintaining skin structure and elasticity. As we age, natural collagen production declines, leading to visible signs of aging. Matrixyl (C16-KTTKS) is a well-known lipopeptide used in cosmetics to stimulate collagen synthesis. However, the precise influence of peptide sequence modifications and counterions on the self-assembly and biological activity of such lipopeptides remains an area for deeper understanding, which could lead to more effective anti-aging formulations.

Researchers investigated the self-assembly, cytocompatibility, and collagen production of two lipopeptides: C16-KTTKS (Matrixyl) and its variant C16-RTTRS, where lysine is substituted with arginine. Both lipopeptides were tested in two salt forms: trifluoroacetate (TFA) and acetate. The study characterized their self-assembly structures (nanotapes vs. micelles) across pH 2-7. Cytocompatibility was assessed in fibroblasts, and collagen production was measured in Human Dermal Fibroblasts (HDFa) at a low concentration of 0.0062 wt%.

C16-KTTKS consistently self-assembled into nanotapes across pH 4-7 and micelles at pH 2, with minimal counterion influence. In contrast, C16-RTTRS exhibited more varied self-assembly: forming substantial spherical micelles with the acetate salt across pH 2-7, but predominantly nanotapes with the TFA salt for pH 4-7. Conditions for hydrogel formation by C16-KTTKS were also identified. Both lipopeptides demonstrated good cytocompatibility with fibroblasts at sufficiently low concentrations. Importantly, both C16-KTTKS and C16-RTTRS stimulated collagen production in HDFa cells at 0.0062 wt%. No significant effect of the counterion was observed on either cell viability or collagen production for either lipopeptide. The results highlight that peptide sequence significantly influences pH-dependent self-assembly, which can be modulated by counterions for specific lipopeptides.

Both C16-KTTKS and C16-RTTRS significantly stimulated collagen production in Human Dermal Fibroblasts (HDFa) at a low concentration of 0.0062 wt%, demonstrating their potent bioactivity.