Nanostructure and Collagen-Stimulating Activity of Cationic Pentapeptide Lipopeptides.

de Mello LR, Castelletto V, Seitsonen J, Hamley IW

Journal of peptide science : an official publication of the European Peptide Society1 Aug 2026

PMID42317129PMCIDPMC13280649DOI10.1002/psc.70111PepBankPUB-42317129

Summary

The self-assembly in aqueous solutions, cytocompatibility, and collagen production of lipopeptide C₁₆-KTTKS and a variant with arginine substitution for lysine, C₁₆-RTTRS, are investigated. C₁₆-KTTKS is known commercially as Matrixyl and is used in cosmetic formulations as it can stimulate collagen production. The self-assembly and conformations and collagen-stimulating effects of the two lipopeptides in two salt forms, trifluoroacetate (TFA) and acetate, are compared. Lipopeptide C₁₆-KTTKS self-assembles into nanotapes based on a multi-bilayer stacking across a pH range pH 4-7 and micelles at pH 2, with little influence of the counterion. In contrast, C₁₆-RTTRS forms a substantial population of spherical micelles for the acetate salt for pH 2-7, but mainly nanotapes for the TFA salt for pH 4-7. Conditions for hydrogel formation by C₁₆-KTTKS were identified. Both lipopeptides show good cytocompatibility to fibroblasts at sufficiently low concentration. The two lipopeptides also stimulate collagen production in Human Dermal Fibroblasts (HDFa) at low concentration (0.0062 wt%). No significant effect of the counterion was noted on cell viability or collagen production. Our results suggest that the peptide sequence influences the pH-dependent self-assembly properties and that this can be modulated for certain lipopeptides by the nature of the counterions.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study7

2 results from studies that gave the peptide. No result from this study comes from people.

01LabIn vitro (cells)Safety outcome
In fibroblasts, Matrixyl showed good cytocompatibility at sufficiently low concentration.
In plain wordsIn cells, Matrixyl showed good compatibility with fibroblasts at sufficiently low concentration.
Peptide
Matrixyl (palmitoyl pentapeptide-4)
Outcome
Not applicableCytocompatibility
Study
n: not reported in source
Fibroblasts
Outcome group
Adverse events · Pharmacology
Studied dose
Dose not stated
Source sentences
Summary
Both lipopeptides show good cytocompatibility to fibroblasts at sufficiently low concentration.
2 context sentences(design, population, supporting numbers)
Summary · context
The self-assembly in aqueous solutions, cytocompatibility, and collagen production of lipopeptide C₁₆-KTTKS and a variant with arginine substitution for lysine, C₁₆-RTTRS, are investigated.
Summary · context
The self-assembly and conformations and collagen-stimulating effects of the two lipopeptides in two salt forms, trifluoroacetate (TFA) and acetate, are compared.
Show in the study text Report a problemFND-4231712904
02LabIn vitro (cells)Activity measurement
In human dermal fibroblasts, Matrixyl stimulated collagen production at 0.0062 wt%.
In plain wordsIn cells, Matrixyl stimulated collagen production in human dermal fibroblasts at 0.0062 wt%.
Peptide
Matrixyl (palmitoyl pentapeptide-4)
Outcome
IncreaseCollagen production
Study
humann: not reported in source
Human Dermal Fibroblasts (HDFa)
Outcome group
Skin and hair · Skin and wound
Studied dose
0.0062 wt%As given in this study (human).
Measurements
Concentration
0.0062 wt%
collagen production
Source sentences
Summary
The two lipopeptides also stimulate collagen production in Human Dermal Fibroblasts (HDFa) at low concentration (0.0062 wt%).
2 context sentences(design, population, supporting numbers)
Summary · context
The self-assembly in aqueous solutions, cytocompatibility, and collagen production of lipopeptide C₁₆-KTTKS and a variant with arginine substitution for lysine, C₁₆-RTTRS, are investigated.
Summary · context
The self-assembly and conformations and collagen-stimulating effects of the two lipopeptides in two salt forms, trifluoroacetate (TFA) and acetate, are compared.
Show in the study text Report a problemFND-4231712905

Studies that did not test the peptide alone5

In this study, Matrixyl (palmitoyl pentapeptide-4) was a lab tool or a carrier, part of a mix, or the subject of a lab method. These results are not evidence about taking Matrixyl (palmitoyl pentapeptide-4).

03LabNot a test of Matrixyl (palmitoyl pentapeptide-4) aloneIn vitro (cells)Safety outcome
In fibroblasts exposed to Matrixyl, the counterion did not significantly affect cell viability.
In plain wordsIn cells exposed to Matrixyl, cell viability did not differ significantly between the TFA and acetate counterions.
Peptide
Matrixyl (palmitoyl pentapeptide-4)
Outcome
No significant changeCounterion effect on cell viability
Study
n: not reported in source
Fibroblasts
Comparator
TFA versus acetate counterion
Outcome group
Adverse events · Pharmacology
Source sentences
Summary
No significant effect of the counterion was noted on cell viability or collagen production.
2 context sentences(design, population, supporting numbers)
Summary · context
The self-assembly in aqueous solutions, cytocompatibility, and collagen production of lipopeptide C₁₆-KTTKS and a variant with arginine substitution for lysine, C₁₆-RTTRS, are investigated.
Summary · context
The self-assembly and conformations and collagen-stimulating effects of the two lipopeptides in two salt forms, trifluoroacetate (TFA) and acetate, are compared.
In this study, Matrixyl (palmitoyl pentapeptide-4) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Matrixyl (palmitoyl pentapeptide-4).
Show in the study text Report a problemFND-4231712906
04LabNot a test of Matrixyl (palmitoyl pentapeptide-4) aloneIn vitro (cells)Activity measurement
In fibroblasts exposed to Matrixyl, the counterion did not significantly affect collagen production.
In plain wordsIn cells exposed to Matrixyl, collagen production did not differ significantly between the TFA and acetate counterions.
Peptide
Matrixyl (palmitoyl pentapeptide-4)
Outcome
No significant changeCounterion effect on collagen production
Study
humann: not reported in source
Human Dermal Fibroblasts (HDFa)
Comparator
TFA versus acetate counterion
Outcome group
Skin and hair · Skin and wound
Source sentences
Summary
No significant effect of the counterion was noted on cell viability or collagen production.
2 context sentences(design, population, supporting numbers)
Summary · context
The self-assembly in aqueous solutions, cytocompatibility, and collagen production of lipopeptide C₁₆-KTTKS and a variant with arginine substitution for lysine, C₁₆-RTTRS, are investigated.
Summary · context
The self-assembly and conformations and collagen-stimulating effects of the two lipopeptides in two salt forms, trifluoroacetate (TFA) and acetate, are compared.
In this study, Matrixyl (palmitoyl pentapeptide-4) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Matrixyl (palmitoyl pentapeptide-4).
Show in the study text Report a problemFND-4231712907
05LabNot a test of Matrixyl (palmitoyl pentapeptide-4) aloneIn vitro (cell-free)Other
In aqueous solutions, Matrixyl formed multilayer nanotapes at pH 4-7 and micelles at pH 2.
In plain wordsIn lab tests, Matrixyl formed nanotapes at pH 4-7 and micelles at pH 2.
Peptide
Matrixyl (palmitoyl pentapeptide-4)
Outcome
Not applicablepH-dependent self-assembly
Study
n: not reported in source
Aqueous lipopeptide solutions
Outcome group
Receptor activity and mechanism · Pharmacology
Source sentences
Summary
Lipopeptide C₁₆-KTTKS self-assembles into nanotapes based on a multi-bilayer stacking across a pH range pH 4-7 and micelles at pH 2, with little influence of the counterion.
2 context sentences(design, population, supporting numbers)
Summary · context
The self-assembly in aqueous solutions, cytocompatibility, and collagen production of lipopeptide C₁₆-KTTKS and a variant with arginine substitution for lysine, C₁₆-RTTRS, are investigated.
Summary · context
The self-assembly and conformations and collagen-stimulating effects of the two lipopeptides in two salt forms, trifluoroacetate (TFA) and acetate, are compared.
In this study, Matrixyl (palmitoyl pentapeptide-4) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Matrixyl (palmitoyl pentapeptide-4).
Show in the study text Report a problemFND-4231712901
06LabNot a test of Matrixyl (palmitoyl pentapeptide-4) aloneIn vitro (cell-free)Other
In aqueous solutions, the counterion had little influence on Matrixyl self-assembly.
In plain wordsIn lab tests, the counterion had little influence on Matrixyl self-assembly.
Peptide
Matrixyl (palmitoyl pentapeptide-4)
Outcome
Not applicableCounterion influence on self-assembly
Study
n: not reported in source
Aqueous lipopeptide solutions
Outcome group
Receptor activity and mechanism · Pharmacology
Source sentences
Summary
Lipopeptide C₁₆-KTTKS self-assembles into nanotapes based on a multi-bilayer stacking across a pH range pH 4-7 and micelles at pH 2, with little influence of the counterion.
2 context sentences(design, population, supporting numbers)
Summary · context
The self-assembly in aqueous solutions, cytocompatibility, and collagen production of lipopeptide C₁₆-KTTKS and a variant with arginine substitution for lysine, C₁₆-RTTRS, are investigated.
Summary · context
The self-assembly and conformations and collagen-stimulating effects of the two lipopeptides in two salt forms, trifluoroacetate (TFA) and acetate, are compared.
In this study, Matrixyl (palmitoyl pentapeptide-4) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Matrixyl (palmitoyl pentapeptide-4).
Show in the study text Report a problemFND-4231712902
07LabNot a test of Matrixyl (palmitoyl pentapeptide-4) aloneIn vitro (cell-free)Other
In lab tests, conditions for Matrixyl hydrogel formation were identified.
In plain wordsIn lab tests, researchers identified conditions for Matrixyl hydrogel formation.
Peptide
Matrixyl (palmitoyl pentapeptide-4)
Outcome
Not applicableHydrogel formation conditions
Study
n: not reported in source
Aqueous lipopeptide solutions
Outcome group
Receptor activity and mechanism · Pharmacology
Source sentences
Summary
Conditions for hydrogel formation by C₁₆-KTTKS were identified.
2 context sentences(design, population, supporting numbers)
Summary · context
The self-assembly in aqueous solutions, cytocompatibility, and collagen production of lipopeptide C₁₆-KTTKS and a variant with arginine substitution for lysine, C₁₆-RTTRS, are investigated.
Summary · context
The self-assembly and conformations and collagen-stimulating effects of the two lipopeptides in two salt forms, trifluoroacetate (TFA) and acetate, are compared.
In this study, Matrixyl (palmitoyl pentapeptide-4) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Matrixyl (palmitoyl pentapeptide-4).
Show in the study text Report a problemFND-4231712903

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Version 2Current
22 Oct 2026, 02:26 UTC
Study results updated
Version 1
21 Oct 2026, 18:59 UTC
First added · source update from Europe PMC

Subjects

Terms as the source lists them.

Publication types

MeSH terms

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