Matrixyl (palmitoyl pentapeptide-4)

Matrixyl is a cosmetic ingredient, palmitoyl pentapeptide-4 (Pal-KTTKS), consisting of the pentapeptide Lys-Thr-Thr-Lys-Ser linked to palmitic acid. Its research consists mainly of in-vitro collagen synthesis studies and small cosmetic studies of skin appearance.

Last reviewed 2026-10-25 by the PeptideWiki editorial team. Editorial policy.

Overview

Matrixyl is the trade name for palmitoyl pentapeptide-4, an INCI-listed cosmetic ingredient previously labeled palmitoyl pentapeptide-3. It consists of the pentapeptide Lys-Thr-Thr-Lys-Ser (KTTKS) attached at its N-terminus to palmitic acid, a 16-carbon fatty acid. KTTKS is a sequence from the propeptide region of type I procollagen, and earlier cell-culture research reported that this small fragment stimulated production of extracellular matrix components by fibroblasts. The palmitoyl group was added to increase lipophilicity and improve association with skin.

Matrixyl belongs to the group of so-called signal peptides in cosmetic science, intended to mimic fragments released during matrix turnover. The research supporting it consists mainly of in-vitro experiments on fibroblast collagen and matrix synthesis, and small cosmetic studies in volunteers measuring wrinkles and skin texture. The name Matrixyl 3000 refers to a different blend of two other palmitoylated peptides. It is a cosmetic ingredient, not a drug.

Compare: Argireline vs Matrixyl.

Structure

Matrixyl is palmitoyl-Lys-Thr-Thr-Lys-Ser-OH (Pal-KTTKS): the pentapeptide KTTKS with a palmitoyl group amide-linked to the N-terminal amine and a free C-terminal acid. The peptide portion is hydrophilic and carries two lysines, while the C16 fatty acyl chain makes the whole molecule amphiphilic, so it can behave like a surfactant and self-assemble in water. The palmitoyl group adds substantially to the mass, so the expected mass of the conjugate differs from that of KTTKS alone. Cosmetic raw material is often supplied as a dilute solution in carriers such as glycerin or other solvents.

Mechanism

The proposed mechanism is that KTTKS acts as a matrikine, a matrix-derived fragment that signals fibroblasts to increase synthesis of extracellular matrix components such as collagen types I and III and fibronectin. This idea comes from fibroblast culture studies; the receptor or pathway through which KTTKS acts has not been clearly identified, and some work has suggested involvement of TGF-β-related signaling. Whether topically applied palmitoyl pentapeptide-4 reaches dermal fibroblasts in active concentrations in intact skin is uncertain.

Research

Collagen synthesis in vitro

Cell-culture studies reported that KTTKS and its palmitoylated form increased production of collagen and other matrix proteins by human dermal fibroblasts. These experiments are the main mechanistic foundation for the ingredient. They are performed at defined concentrations on isolated cells and do not establish what happens after application to intact skin, where penetration, metabolism and formulation all intervene. Signaling responses in two-dimensional fibroblast cultures may also differ from those in three-dimensional skin tissue.

Cosmetic studies of wrinkles

Small studies in volunteers, often vehicle-controlled and sometimes split-face, have assessed periorbital wrinkles, fine lines and skin texture using image analysis or profilometry after weeks of topical use of palmitoyl pentapeptide-4 preparations. Some reported improvements relative to vehicle. These trials are modest in size and duration, frequently industry-sponsored, and assess cosmetic appearance rather than medical outcomes. Results are often reported in technical or trade publications, limiting independent appraisal of their methods.

Skin penetration and formulation

Permeation studies have examined how palmitoylation affects skin uptake, generally finding that the lipid conjugate penetrates better than unmodified KTTKS, while overall delivery to the dermis remains limited. The amphiphilic nature of the molecule also affects formulation, stability and self-assembly behavior. Delivery systems and carriers have been investigated, and the formulation can substantially influence any observed cosmetic effect. These questions make it difficult to attribute any observed change to the peptide itself.

Evidence quality

Matrixyl has a coherent mechanistic hypothesis and supportive in-vitro data, but the human evidence consists of small cosmetic studies with limited independent replication. It is often compared with retinoids in marketing contexts, but robust head-to-head evidence is scarce. Researchers should describe it as a cosmetic signal peptide with mainly in-vitro support and modest cosmetic-study evidence. Long-term data on cosmetic outcomes are lacking.

Regulatory status

Matrixyl is a cosmetic ingredient listed under the INCI name palmitoyl pentapeptide-4 (formerly palmitoyl pentapeptide-3). It is not an FDA-approved drug and is not intended to treat any condition. In the United States, products containing it are regulated as cosmetics, and claims that a product affects body structure or function can cause it to be regarded as a drug. Cosmetic ingredient regulations differ in other jurisdictions.

Status changes often. See the regulatory tracker for dated updates.

Quality and identity testing

A certificate of analysis should confirm identity by mass spectrometry against the expected mass of the palmitoylated conjugate, not of KTTKS alone, and report purity by HPLC with the chromatogram. Because the molecule is amphiphilic, reverse-phase methods need appropriate gradients and may show broad peaks or carryover; unpalmitoylated KTTKS and incompletely or over-acylated species, such as palmitoylation on a lysine side chain, are relevant impurities. When the ingredient is supplied as a dilute solution, the COA should state peptide concentration separately from purity. Matrixyl 3000 is a different material and should not be substituted.

For a walkthrough of each section of a certificate, see how to read a COA.

Storage and stability

Store solid palmitoyl pentapeptide-4 sealed at -20 °C or in refrigerated conditions as indicated on its documentation, protected from light and moisture, and let containers reach room temperature before opening. Its amphiphilic character means solubility in plain water can be limited and it may form micelles or aggregates; co-solvents are often used for stock solutions. Mix gently to avoid foaming, aliquot solutions for lab use, store them cold, and avoid repeated freeze-thaw cycles.

Download the Matrixyl (palmitoyl pentapeptide-4) data sheet (PDF): sequence, masses, expected MS ions and handling on one printable page.

Latest research

Frequently asked questions

Related compounds

• GHK-Cu

  GHK-Cu is the copper(II) complex of GHK (glycyl-histidyl-lysine), a tripeptide found in human plasma. It is widely used as a cosmetic ingredient and studied in cell, animal and small human skin studies.

• Argireline (acetyl hexapeptide-8)

  Argireline is a cosmetic ingredient, acetyl hexapeptide-8 (formerly acetyl hexapeptide-3), a six-residue peptide modeled on the N-terminal region of the SNARE protein SNAP-25. It has been studied in vitro and in small cosmetic trials of expression lines.

• Snap-8

  Snap-8, or acetyl octapeptide-3, is a synthetic eight-residue cosmetic peptide, Ac-EEMQRRAD-NH2, modeled on the N-terminal region of the SNARE protein SNAP-25. It is studied mainly in vitro and in cosmetic formulation research.

References

1. PubMed: all indexed literature on Matrixyl (palmitoyl pentapeptide-4)
2. ClinicalTrials.gov: registered studies mentioning Matrixyl (palmitoyl pentapeptide-4)