Collagen Stimulating Lipopeptides for Cosmetic Applications
Submitting InstitutionUniversity of Reading
Unit of AssessmentChemistry
Summary Impact TypeTechnological
Research Subject Area(s)
Biological Sciences: Biochemistry and Cell Biology
Medical and Health Sciences: Pharmacology and Pharmaceutical Sciences
Summary of the impact
The multi-million pound skincare industry has benefitted greatly from
research carried out since 2009 at Reading, demonstrating for the first
time that an ingredient in some anti-ageing face creams can genuinely
increase the amount of collagen produced by skin cells, thereby removing
the appearance of wrinkles. The research investigated the nanostructure of
the lipopeptide known as Matrixyl and how changes to its environment and
composition affect its structure and activity. These findings received
widespread media coverage in the UK and abroad, leading to noticeable
increases in sales of Matrixyl-containing products by Procter and Gamble
and enhancing the business of the UK-based SME Forme Laboratories,
who have developed a new line of effective skincare products for
menopausal women, based on the Reading results.
Ian Hamley, Diamond Professor of Physical Chemistry (2005-present), has
been investigating the nanostructure of the lipopeptide C16-KTTKS
(Matrixyl) since 2009. Matrixyl is an ingredient found in a number of
commercial face-creams and Hamley's group has demonstrated its ability to
increase the amount of collagen produced by fibroblasts — cells found in
connective tissues such as skin — by 70%. Collagen is the principal
protein that contributes to the strength and elasticity of skin.
While Hamley's research on C16-KTTKS has inherent implications
for skin-care products, his primary interest is in the development of next
generation biomaterials for assisting wound healing and regenerative
medicine, focusing on strategies to increase production of collagen, the
main structural protein in mammalian connective tissue. The peptide KTTKS
has been previously shown to promote and stimulate collagen production. In
2000, a French biotechnology company (Sederma) added a 16-carbon lipid
chain to KTTKS to confer enhanced stability in vivo, and thus increase its
bioavailability by increasing resistance to enzymatic degradation. This lipopeptide
or peptide amphiphile, (PA) C16KTTKS, was registered
under the trade name Matrixyl.
Investigating the nanostructure of Matrixyl
The way in which molecules of Matrixyl-like peptides aggregate depends
upon the length of the lipid tail and the surrounding chemical
environment, both of which can influence peptide activity. In 2009, Hamley
and Castelletto (Research Fellow at Reading, 2005-present) began studying
the nanostructure of Matrixyl to better understand its mode of action.
Despite its widespread commercial use, no previous studies of the
physico-chemical properties of Matrixyl had been undertaken. Castelletto
and Hamley (at Reading) led the research, although some experiments were
also carried out in specialist facilities at the Israel Institute of
Technology (Technion). Techniques including atomic force microscopy and
pyrene fluorescence microscopy were used to reveal the aggregated
nanostructure of Matrixyl. In 2010, the team reported that, unlike
compounds of similar size that form cylindrical nanostructures, Matrixyl
forms flattened aggregates termed "nanotapes". The molecules were
stacked in a way that suggested the structure itself may be important in
stimulating collagen production.
How the chemical environment influences structure
In skincare products, Matrixyl is formulated with surfactants such as
emulsifiers or dispersants, and it was of fundamental interest to
understand how these materials affect self-assembly of Matrixyl and
ultimately its biomedical activity. Between 2011 and 2012, Hamley's group
demonstrated that a non-ionic polymeric surfactant (Pluronic P-123) can be
used to prepare solutions of Matrixyl without disrupting its self-assembly
characteristics or altering its activity.  They also examined the
influence of the anionic surfactant SDS on Matrixyl, finding that, due to
electrostatic forces, different nanostructures are formed depending on the
amount of SDS added, resulting in modification of its macroscopic
characteristics such as a change in morphology from sol to gel.  In
2013, the team found that changes in pH also affected self-assembly of
Matrixyl. At pH2, the Matrixyl formed spherical micelles with the
hydrophobic tails inside, whilst at pH3, they assembled into tape-like
structures and, at pH4, they formed right-hand twisted fibrous structures.
Modifying the lipid tail
The Reading group also investigated how the length of the lipid tail
altered the self-assembly of Matrixyl-type peptide amphiphiles, using
techniques including circular dichroism and small angle X-ray scattering,
to understand how tail length affected their physico-chemical properties.
They found that skin-permeability increased with longer lipid tails, with
a C14 tail formulation estimated to be 3.8 times less permeable
than a C16 tail and a C16 tail 3.8 times less
permeable than a C18 tail.  Therefore it seemed possible at
this stage that a PA with a longer lipid tail could have an enhanced
collagen-stimulating effect due to a higher skin-permeability, with
implications not only in regenerative medicine but also for the skin-cream
Proving that Matrixyl stimulates collagen production
In 2013, Hamley and colleagues reported that Matrixyl stimulates collagen
production in human skin and corneal cells in a concentration-dependent
manner, indicating that self-assembly and collagen production are
interrelated.  The finding was based on nanostructural analyses carried
out by Roanne Jones (PhD student, 2010-2013) who was co-supervised by
Hamley and Dr Che Connon (Lecturer/Associate Professor in Pharmacy,
2007-date) at Reading. This was the first independent demonstration of the
stimulation of collagen production by C16-KTTKS / Matrixyl.
References to the research
(Citations retrieved from Scifinder on 24/10/13)
Publications have been internally reviewed and assessed as of at least 2*
quality. Outputs marked as * are suggested to assessed quality of
 Castelletto, V., Hamley, I.W., Perez, J., Abezgauz, L. & Danino,
D. (2010) Fibrillar superstructure from extended nanotapes formed by a
collagen-stimulating peptide. Chem.l Commun., 46 (48): 9185 -
9187. DOI: 10.1039/c0cc03793a. (Cited 18 times).
 Dehsorkhi, A., Castelletto, V., Hamley, I.W. & Lindner, P. (2012)
Influence of a non-ionic amphiphile copolymer on the self-assembly of a
peptide amphiphile that forms nanotapes. Soft Matter, 8 (33):
8608-8615. DOI: 10.1039/c2sm25990g.
 *Castelleto, V., Hamley, I.W., Adamcik, J., Mezzenga, R. &
Gummel, J. (2012) Modulating self- assembly of a nanotape-forming peptide
amphiphile with an oppositely charged surfactant. Soft Matter, 8
(1): 217-226. DOI: 10.1039/c1sm06677c. (Cited 20 times).
 Dehsorkhi, A., Castelletto, V., Hamley, I.W., Adamcik, J. &
Mezzenga, R. (2013) The effect of pH on the self-assembly of a collagen
derived peptide amphiphile. Soft Matter, 9 (26):6033- 6036. DOI:
 Palladino, P., Castelletto, V., Dehsorkhi, A., Stetsenko, D. &
Hamley, I.W. (2012) Conformation and Self-association of peptide
amphiphiles based on the KTTKS Collagen sequence. Langmuir 28
(33): 12209 - 12215. DOI: 10.1021/la302123h. (Cited 4 times).
 *Jones, R.R., Castelletto, V., Connon, C.J. & Hamley, I.W. (2013)
Collagen stimulating effect of peptide amphiphile C16-KTTKS on
human fibroblasts. Mol. Pharmaceutics, 10 (3): 1063-1069. DOI:
10.1021/mp300549d. (Cited 1 time).
Grants: This work was funded by BBSRC grants to Prof. Hamley:
BB/I008187/1 "Polymeric Templates for Corneal Stem Cells" (with Dr Che
Connon) and BB/J019836/1 "Smart Materials for Wound Healing: A New Fast
Acting In Situ Method to Treat Skin and Eye Wounds" (with Prof. Adrian
Williams and Dr Che Connon).
Details of the impact
This very recent work has informed the public about the scientific basis
of the reported activity of peptide-based skincare treatments, with high
levels of media coverage stimulating public interest and awareness of the
underpinning science. This is important since many previous cosmetic skin
care claims have been based on absent or insubstantial scientific
evidence. The work has already had substantial impact on industry — the
UK-based SME Forme Laboratories has, for example, launched a new
skincare product for menopausal women, "Stratum C", based on this work. Procter
and Gamble has experienced increased sales of "Olay Regenerist", an
existing product range containing the key KTTKS peptide, and other
companies in the cosmetics field have sought collaboration with Prof.
Hamley. Between 2010 and 2013, the research conducted at Reading received
considerable media attention in popular science magazines, national
newspapers, national radio, industry publications and women's magazines.
The media linked this rigorous, independent science with existing products
in the multi-million pound skincare market, bringing genuine evidence of
product efficacy to fact-hungry consumers. This not only increased public
awareness of the science, but has had a major impact on the entire
Informing the public through media
Hamley's research publications [1 - 6] generated a series of media
publications that reached millions of people in the UK and across the
world. Examples include:
- "The nano-secret of youthful skin", New Scientist (21 November
2010) [Online audience of over 2.3 million unique users]
- Macrae, F. & Kisiel, R., "Anti-wrinkle creams that really
work...but only with a magic ingredient", Daily Mail (6 March
2013) [42 million UK unique browsers/month; 129 million unique browsers
- "Scientists find `miracle ingredient' in anti-wrinkle creams", Huffington
Post UK (7 March 2013) [4.8 million unique users]
- "Research proves Matrixyl CAN make you look younger!", Woman
Magazine [over 600,000 people weekly — print, online and social
- "Key to tissue growth may be in anti-wrinkle cream", Phys.org
(1 November 2010) [>1.5 million unique monthly users]
- "Scientists claim to discover "anti-wrinkle secret", ITV News
(6 Mar 2013) [1.5 million unique monthly users]
- "Anti-wrinkle creams actually work!", The Times of India (20
Mar 2013) [average daily readership over 7.6 million]
- "There's the rub with anti-wrinkle creams", The Australian Weekend
Magazine (6 Apr 2013) [weekly readership ~700,000]
- "Research suggests a specific peptide has enhance anti-ageing
properties", CosmeticsDesign- Europe.com (7 March 2013)
[highest-read European news website in the cosmetics industry]
- BBC Radio 4 — You and Yours, 21 Jun 2013
The Daily Mail and ITV News both quoted the Fashion and Beauty Editor of
the Press Association as saying: `Anti-ageing creams frequently boast
about being packed full of peptides, but aren't specific as to which
one. Now the secret's out and there's some scientific evidence for its
collagen- boosting properties, women will be rushing to find out if it's
in their anti-ageing potion. It's likely that brands with products that
do contain Matrixyl will start shouting about it too if the "miracle"
peptide becomes the new buzz word in beauty. There was a stampede at
Boots in 2007 for No 7 Protect & Perfect Beauty Serum after a BBC2
Horizon programme scientifically backed the [Matrixyl containing] lotion.....'.
Media attention leads to increased sales of existing skin products
The UK skincare market was valued at more than £1.7 billion in 2011 and is
predicted to be worth more than £1.9 billion by the end of 2016. Facial
care is worth 58.8% of the total skincare market value [Datamonitor —
"Skincare in the UK to 2016" published 22/11/2012]. Consumers are becoming
more appearance conscious, with a 7% increase between 2008 and 2011 in the
number of global consumers attaching importance to "looking good"
[Datamonitor — "The Future of Skincare: Consumption trends and product
preferences", published 07/10/2011]. Within such a competitive and
high-value industry, every market advantage is of huge benefit to
As a result of the media attention, several women's magazines ran
articles that promoted skin products containing the `miracle ingredient',
Matrixyl, including Cosmopolitan [b] and Woman [c] , with
the latter referring directly to the research at Reading.
One of the products mentioned is the Olay brand, a global market leader
[d], produced by Procter and Gamble (P&G). Following the research
publication  and the associated media coverage, P&G benefitted from
a significant boost in sales of this product in the UK. Exact sales
figures are confidential, but a spokesperson from the Procter and Gamble
London Innovation Centre [d,e] said there was a "noticeable increase in
sales", as quoted below :
"The Molecular Pharmaceutics paper and subsequent mention in the Daily
Mail (Anti-wrinkle creams that really work") led to a high level of
media interest and actual coverage across print and online publications
and social media platforms such as Twitter. The specific mention of an
Olay Regenerist product containing Matrixyl led to a noticeable increase
in sales of this product."
"The fact that the original Molecular Pharmaceutics paper appeared in a
peer-reviewed science publication certainly gave great credibility to
the following media coverage, although none of the mentioned cosmetic
products had been part of the research. Media and consumers alike are
hungry for independent, believable information and we have seen direct
correlations between media coverage and sales numbers in this particular
case as well in previous examples. This is way [sic] research
partnerships and scientific credentialling are key strategies for Olay
and other P&G businesses."
Industry invests in research and development and new products
The research has also impacted on small and medium enterprises working in
the skin care area. Forme Laboratories was recently established by a team
of entrepreneurs. Hamley's research influenced their approach to
developing a new range of skin care products, Stratum C, which are
scientifically formulated for the skin of menopausal women using Matrixyl.
Hamley is featured on the company website, explaining the science behind
their products [f]. The CEO of Forme Laboratories [g] stated that Hamley's
research findings  stimulated their investment in the development of
new products and further research:
"We became aware of the work of Professor Hamley and the University of
Reading on peptides and collagen production through the online coverage.
This contributed to the development of a new product called StratumC
aimed directly at menopausal women to stimulate collagen growth during a
period of compromised cellular function. We hope to use the basic
science as a foundation for further research and to optimise the product
with the help of Professor Hamley and the University."
Stratum C products are manufactured in the US, and are available online
from the UK-based Forme Laboratories, with a full treatment regime for
three months costing £120.
Sources to corroborate the impact
[a] MacRae, F. & Kisiel, R. (5 March 2013) "Anti-wrinkle creams that
really work....but only with a magic ingredient", Daily Mail <http://www.dailymail.co.uk/health/article-2288955/Anti-wrinkle-creams-really-work--magic-ingredient.html>
[b] (2013) "Cosmo's 10 best wonder creams", Cosmopolitan
that the world's number one woman's magazine was promoting products
containing Matrixyl, with direct mention of this ingredient and reference
to supporting science behind it.
[c] (2013) "Research proves Matrixyl CAN make you look younger!", Woman
Promotes Matrixyl-containing products and refers directly to research by
the University of Reading.
[d] P&G (2 January 2013) "Olay Regenerist", P&G connect +
that this matrixyl-containing product is a leading product.
[e] Scientific Communications, Global Olay and EMEA Skin Care, Procter
and Gamble London Innovation Centre.
[f] "How Stratum C works", Stratum C, The Science <http://www.stratumc.com/the-science/>
Hamley's research directly to this new product line of skincare for
[g] Director, Forme Laboratories — Contact details provided.