Known by various names, including palmitoyl pentapeptide-4 and palmitoyl pentapeptide-3, Matrixyl appears to exhibit a unique structure characterized by its conjugation with palmitoyl. This structural modification is speculated to enhance its delivery across the skin and fortify its stability against enzymatic degradation by skin proteases, potentially yielding in more invigorated and healthy skin.⁽¹⁾

At the heart of Matrixyl’s allure lies its synthetic composition and its supposed potential to stimulate Collagen production within the skin. As a matrikine, Matrixyl appears to act as a messenger peptide, possibly orchestrating cell activities by interacting with specific receptors. Collagen, the structural protein responsible for skin’s firmness and elasticity, is said to diminish with age, resulting in the formation of fine lines and wrinkles. Matrixyl, by potentially promoting collagen synthesis, appears to hold the promise of restoring the skin’s resilience and reducing the visible markers of aging. 

This lipopeptide, composed of fatty acids and amino acids, is also said to possess the intriguing characteristic of being a synthetic isomer. An isomer, in this context, refers to a molecule with an identical structure to another molecule but comprised of different atomic components. Within Matrixyl lies its active component known as micro-collagen, yet another peptide that possibly contributes to its potential action. 

In this article, we delve deeper into the science of Matrixyl, exploring its mechanism of action, ongoing research, and potential.

Matrixyl Mechanism of Action

Studies suggest that the Matrixyl peptide operates as a transformative force within the skin, possibly offering a multifaceted mechanism of action that appears to address both Wound Healing and the intricate processes behind wrinkle formation. 

Its discovery emerged from dual strands of dermatological research, rooted in the quest to accelerate skin wound healing and the investigation into the origins of wrinkles.

Matrixyl, akin to copper peptides, is speculated to exert its influence by stimulating the lower “matrix”  layers of the skin, inducing them to embark on a regenerative journey. At the core of this mechanism are specialized cells known as fibroblasts, which are said to play a pivotal role in knitting together the skin’s wounds. As time progresses, the healing of wounds tends to slow down, a phenomenon attributed in part to the gradual decline in fibroblasts’ capacity for collagen production.⁽²⁾

One of Matrixyl’s remarkable attributes appears to be its ability to awaken the dormant potential within these fibroblasts, reportedly prompting them to re-engage in the synthesis of essential structural components of the skin, primarily collagen and fibronectin. Matrixyl, by virtue of its action on fibroblasts, appears to potentially counter this natural aspect of the aging process.

Research Studies

Matrixyl Peptide and Collagen Production

Matrixyl’s potential as a signal peptide fragment of the C-terminal propeptide of type I collagen has garnered attention amongst contemporary researchers.⁽⁵⁾ This peptide is believed to function by transmitting signals to fibroblasts, and reportedly “stimulates feedback regulation of new collagen synthesis and ECM proteins.” 

Fibroblasts, integral cells within connective tissue, play a vital role in crafting and upholding the ECM—a complex mesh of proteins and carbohydrates that provides structural support to tissues and organs. The ECM’s cornerstone proteins, including collagens, elastins, fibronectins, and laminins, contribute to tissue integrity and shape maintenance. Collagen, as the primary structural protein, imparts tensile strength to these structures. In the context of wound healing, fibroblasts emerge as the architects of repair, depositing fresh collagen fibers to replace damaged tissue.

Researchers have postulated that Matrixyl’s capacity to stimulate collagen production exhibits concentration-dependent behavior, closely linked to the critical aggregation concentration, implying a correlation between self-assembly and collagen production.⁽⁴⁾ This self-assembly process encompasses diverse interactions, including hydrogen bonds, electrostatic forces, hydrophobic interactions, aromatic bonding (π–π stacking), and van der Waals forces. These intricate mechanisms shed light on the profound potential of Matrixyl in fostering fibroblast rejuvenation.

Matrixyl Peptide and Scar Reduction

In a noteworthy investigation⁽⁵⁾, Matrixyl’s potential impact on fibroblast contractility and its role in scar formation were scrutinized. 

Based on the study results, it appeared that Matrixyl may have effectively downregulated the expression of α-SMA (alpha-smooth muscle actin) and hindered the trans-differentiation of fibroblasts into myofibroblasts. α-SMA is a protein typically found in smooth muscle cells within blood vessels and organs like the intestines and bladder. It is also expressed by specialized cells known as myofibroblasts, pivotal players in wound healing and tissue repair. 

In the context of fibrotic scarring, the heightened expression of α-SMA by myofibroblasts is linked to excessive collagen deposition and the formation of scar tissue. Matrixyl’s speculated potential in modulating these processes holds promise for scar reduction and improved skin healing.

Matrixyl Peptide and Anti-Wrinkle Potential

In a notable clinical trial involving 93 female participants aged 35-55, Matrixyl-infused moisturizer was applied to one side of the face, while a placebo served as a control on the other side over a 12-week period.⁽⁶⁾ Encouragingly, the peptide appeared to exhibit excellent tolerability and demonstrated significant wrinkle and fine-line reduction compared to the placebo. Self-assessment evaluations further corroborated improvements in various facial parameters.

Crow’s feet, charmingly referred to as laughter lines, manifest as wrinkles at the outer corners of the eyes with age, stemming from repetitive facial muscle movement and diminishing skin elasticity. In a clinical study focusing on 21 female subjects grappling with crow’s feet, Matrixyl was introduced topically to the periorbital area twice daily for eight weeks.⁽⁷⁾ Reportedly, Matrixyl appeared to outperform other peptides and the placebo, as discerned from comprehensive data analysis, clinical images, and self-assessment questionnaires, further supporting the peptide’s potential.

Another investigation sought to unravel Matrixyl’s potential in enhancing overall skin smoothness and diminishing the appearance of periorbital wrinkles.⁽⁸⁾ In this rigorous double-blind, randomized, controlled split-face study involving women aged 30-70 with moderate to distinct periorbital wrinkles, the peptide reportedly exhibited notable progress within just four weeks. Researchers observed enhanced periorbital skin smoothness and a reduction in the apparent depth of more pronounced wrinkles.

Matrixyl Peptide and Tissue Repair

An animal-based investigation delved into the potential of Matrixyl to enhance the process of wound healing. The study involved the categorization of animals into seven distinct groups, closely monitored over a span of 21 days.⁽⁹⁾ Encouraging findings indicated that Matrixyl may exert a beneficial influence on wound healing, particularly evident in groups exposed to higher concentrations of Matrixyl when compared to a positive control group. Research suggests a possible notable enhancement in wound healing, with macroscopic results revealing improvements ranging from 63.5% to 81.81% in the experimental groups, as opposed to the negative control group.

References:

1. Choi, Y. L., Park, E. J., Kim, E., Na, D. H., & Shin, Y. H. (2014). Dermal Stability and In Vitro Skin Permeation of Collagen Pentapeptides (KTTKS and palmitoyl-KTTKS). Biomolecules & therapeutics, 22(4), 321–327. https://doi.org/10.4062/biomolther.2014.053 
2. MatrixylTM https://inci.guide/peptides/matrixyltm 
3. Errante, F., Ledwoń, P., Latajka, R., Rovero, P., & Papini, A. M. (2020). Cosmeceutical Peptides in the Framework of Sustainable Wellness Economy. Frontiers in chemistry, 8, 572923. https://doi.org/10.3389/fchem.2020.572923 
4. Jones, R. R., Castelletto, V., Connon, C. J., & Hamley, I. W. (2013). Collagen stimulating effect of peptide amphiphile C16-KTTKS on human fibroblasts. Molecular pharmaceutics, 10(3), 1063–1069. https://doi.org/10.1021/mp300549d 
5. Park H, An E, Cho Lee AR. Effect of Palmitoyl-Pentapeptide (Pal-KTTKS) on Wound Contractile Process in Relation with Connective Tissue Growth Factor and α-Smooth Muscle Actin Expression. Tissue Eng Regen Med. 2017 Jan 19;14(1):73-80. https://link.springer.com/article/10.1007/s13770-016-0017-y 
6. Robinson, L. R., Fitzgerald, N. C., Doughty, D. G., Dawes, N. C., Berge, C. A., & Bissett, D. L. (2005). Topical palmitoyl pentapeptide provides improvement in photoaged human facial skin. International journal of cosmetic science, 27(3), 155–160. https://doi.org/10.1111/j.1467-2494.2005.00261.x 
7. Aruan, R. R., Hutabarat, H., Widodo, A. A., Firdiyono, M. T. C. C., Wirawanty, C., & Fransiska, L. (2023). Double-blind, Randomized Trial on the Effectiveness of Acetylhexapeptide-3 Cream and Palmitoyl Pentapeptide-4 Cream for Crow’s Feet. The Journal of clinical and aesthetic dermatology, 16(2), 37–43. https://pubmed.ncbi.nlm.nih.gov/36909866/ 
8. Kaczvinsky, J. R., Griffiths, C. E., Schnicker, M. S., & Li, J. (2009). Efficacy of anti-aging products for periorbital wrinkles as measured by 3-D imaging. Journal of cosmetic dermatology, 8(3), 228–233. https://doi.org/10.1111/j.1473-2165.2009.00444.x 
9. Kachooeian, M., Mousivand, Z., Sharifikolouei, E., Shirangi, M., Firoozpour, L., Raoufi, M., & Sharifzadeh, M. (2022). Matrixyl Patch vs Matrixyl Cream: A Comparative In Vivo Investigation of Matrixyl (MTI) Effect on Wound Healing. ACS omega, 7(28), 24695–24704. https://doi.org/10.1021/acsomega.2c02592