A palmitoylated pentapeptide (Pal-KTTKS) that is one of the most commercially successful cosmetic peptides. It mimics a collagen fragment that signals fibroblasts to produce new collagen. Found in thousands of anti-aging skincare products worldwide.
Matrixyl (palmitoyl pentapeptide-4, Pal-KTTKS) is a lipopeptide consisting of the pentapeptide KTTKS (Lys-Thr-Thr-Lys-Ser) conjugated to palmitic acid (C16 fatty acid) for skin penetration. Developed by Sederma (now part of Croda), it was introduced in 2000 and quickly became one of the most widely used anti-aging peptides in cosmetics.
The KTTKS sequence is a fragment of collagen type I pro-peptide. When collagen is degraded (as in aging or UV damage), these fragments are released and act as matrikines — signaling molecules that tell fibroblasts 'collagen has been broken down, make more.' Matrixyl mimics this natural signal.
Matrixyl signals through the matrikine pathway. When collagen is degraded by matrix metalloproteinases (MMPs), specific fragments like KTTKS are released. These fragments bind to cell surface receptors on fibroblasts, triggering TGF-β signaling and stimulating new extracellular matrix protein production. By applying synthetic KTTKS, Matrixyl mimics this degradation signal without actual collagen damage, tricking fibroblasts into producing new collagen.
| Pathway | Effect | Significance |
|---|---|---|
| Matrikine signaling | KTTKS fragment activates fibroblast collagen production | Mimics natural collagen turnover signal |
| Collagen I/III synthesis | Upregulates procollagen gene expression | Increases dermal collagen density and skin thickness |
| Fibronectin stimulation | Increases fibronectin production | Improves extracellular matrix organization |
| MMP modulation | May reduce excessive MMP activity | Slows collagen degradation while promoting synthesis |
| Palmitoyl delivery | C16 fatty acid enables skin penetration | Crosses stratum corneum to reach dermal fibroblasts |
| Study | Design | Findings | Level |
|---|---|---|---|
| Wrinkle reduction | Double-blind, n=93, 12 weeks | Matrixyl cream reduced wrinkle depth and volume by up to 68% vs placebo (Sederma study) | Level II |
| Collagen synthesis | In vitro, fibroblast culture | Pal-KTTKS increased collagen types I, III, and IV production in a dose-dependent manner | Preclinical |
| Comparison to retinol | Split-face study | Matrixyl showed comparable wrinkle reduction to retinol with less irritation | Level II-III |
| Skin thickness | Clinical study with ultrasound | Increased dermal thickness after 4 months of topical application | Level II |
Excellent topical safety: Decades of cosmetic use with no significant adverse effects. Non-irritating, non-sensitizing in clinical testing.
No systemic effects: Topical application delivers peptide locally to skin. No measurable systemic absorption.
Stable in formulations: Palmitoylation improves both skin penetration and formulation stability.
| Jurisdiction | Status |
|---|---|
| FDA | Not regulated as a drug. Classified as a cosmetic ingredient. |
| EU | Listed in CosIng database as approved cosmetic ingredient |
| INCI name | Palmitoyl Pentapeptide-4 |
| Market | Found in thousands of skincare products from mass-market to luxury |