Valeria Castelletto

University of Reading, Reading, England, United Kingdom

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Publications (140)509.65 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Amyloid fibrils are formed by a model surfactant-like peptide (Ala)10-(His)6 containing a hexa-histidine tag. This peptide undergoes a remarkable two-step self-assembly process with two distinct critical aggregation concentrations (cacs), probed by fluorescence techniques. A micromolar range cac is ascribed to the formation of pre-fibrillar structures, whereas a millimolar range cac is associated with the formation of well defined but more compact fibrils. We examine the labelling of these model tagged amyloid fibrils using Ni-NTA functionalized gold nanoparticles (Nanogold). Successful labelling is demonstrated via electron microscopy imaging. The specificity of tagging does not disrupt the β-sheet structure of the peptide fibrils. Binding of fibrils and Nanogold is found to influence the circular dichroism associated with the gold nanoparticle Plasmon absorption band. These results highlight a new approach to the fabrication of functionalized amyloid fibrils and the creation of peptide/ nanoparticle hybrid materials.
    Biomacromolecules 08/2014; · 5.37 Impact Factor
  • Ashkan Dehsorkhi, Valeria Castelletto, Ian W. Hamley
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    ABSTRACT: The self-assembly of several classes of amphiphilic peptides is reviewed, and selected applications are discussed. We discuss recent work on the self-assembly of lipopeptides, surfactant-like peptides and amyloid peptides derived from the amyloid-β peptide. The influence of environmental variables such as pH and temperature on aggregate nanostructure is discussed. Enzyme-induced remodelling due to peptide cleavage and nanostructure control through photocleavage or photo-cross-linking are also considered. Lastly, selected applications of amphiphilic peptides in biomedicine and materials science are outlined. © 2014 The Authors. Journal of Peptide Science published by European Peptide Society and John Wiley & Sons, Ltd.
    Journal of Peptide Science 04/2014; · 2.07 Impact Factor
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    ABSTRACT: We examine the self-assembly of a peptide A6H comprising a hexa-alanine sequence A6 with a histidine (H) "head group", which chelates Zn2+ cations. We study the self assembly of A6H and binding of Zn2+ ions in ZnCl2 solutions, under acidic and neutral conditions. A6H self assembles in nanotapes held together by a β-sheet structure in acidic aqueous solutions. By dissolving A6H in acidic ZnCl2 solutions, the carbonyl oxygen atoms in A6H chelate the Zn2+ ions, and allow for β-sheet formation at lower concentrations, consequently reducing the onset concentration for nanotape formation. A6H mixed with water or ZnCl2 solutions under neutral conditions produce short sheets or pseudocrystalline tapes respectively. The imidazole ring of A6H chelates Zn2+ ions in neutral solutions. The internal structure of nanosheets and pseudocrystalline sheets in neutral solutions is similar to the internal structure of A6H nanotapes in acidic solutions. Our results show that is possible to induce dramatic changes in the self assembly and chelation sites of A6H, by changing the pH of the solution. However, it is likely that the amphiphilic nature of A6H determines the internal structure of the self assembled aggregates independent from changes in chelation.
    Biomacromolecules 12/2013; · 5.37 Impact Factor
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    ABSTRACT: We investigate the properties of an antimicrobial surfactant-like peptide (Ala)6(Arg), A6R, containing a cationic headgroup. The interaction of this peptide with zwitterionic (DPPC) lipid vesicles is investigated using a range of microscopic, X-ray scattering, spectroscopic and calorimetric methods. The β-sheet structure adopted by A6R is disrupted in the presence of DPPC. A strong effect on the small-angle X-ray scattering profile is observed: the Bragg peaks from the DPPC bilayers in the vesicle walls are eliminated in the presence of A6R and only bilayer form factor peaks are observed. All of these observations point to the interaction of A6R with DPPC bilayers. These studies provide insight into interactions between a model cationic peptide and vesicles, relevant to understanding the action of antimicrobial peptides on lipid membranes. Notably, peptide A6R exhibits antimicrobial activity without membrane lysis.
    Langmuir 10/2013; · 4.38 Impact Factor
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    ABSTRACT: Queuing up: Molecular orientation within macroscopically aligned nanotubes of the peptide AAAAAAK can be studied by solid-state NMR and IR spectroscopy. Line shape analysis of the NMR spectra indicates that the peptide NH bonds are tilted 65-70° relative to the nanotube long axis. Re-evaluation of earlier X-ray fiber diffraction data suggests that the peptide molecules are hydrogen-bonded in a helical arrangement along the nanotube axis.
    Angewandte Chemie International Edition 08/2013; · 11.34 Impact Factor
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    ABSTRACT: The self-assembly of three cosmetically-active peptide amphiphiles C16-GHK, C16-KT and C16-KTTKS (C16 denotes a hexadecyl, palmitoyl chain) used in commercial skin care products is examined. A range of spectroscopic, microscopic and X-ray scattering methods is used to probe the secondary structure, aggregate morphology and the nanostructure. Peptide amphiphile (PA) C16-KTTKS forms flat tapes and extended fibrillar structures with high β-sheet content. In contrast, C16-KT and C16-GHK exhibit crystal-like aggregates with, in the case of the latter PA, lower β-sheet content. All three PA samples show spacings from bilayer structures in small-angle X-ray scattering profiles, and all three have similar critical aggregation concentrations, this being governed by the lipid chain length. However, only C16-KTTKS is stained by Congo red, a diagnostic dye used to detect amyloid formation, and this PA also shows a highly aligned cross-β X-ray diffraction pattern consistent with the high β-sheet content in the self-assembled aggregates. These findings may provide important insights relevant to the role of self-assembled aggregates on the reported collagen-stimulating properties of these PAs.
    Langmuir 07/2013; · 4.38 Impact Factor
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    ABSTRACT: Transitions in nanostructure driven by pH are observed for a self-assembling peptide amphiphile (PA) with a cationic pentapeptide headgroup. At pH 3, the PA forms flat tape-like structures, while at pH 4 the PA assembles into twisted right handed structures. These twisted structures transform again to flat tape-like structures at pH 7. In complete contrast, spherical micelles are observed at pH 2. These changes in response to pH may be relevant to biological and pharmaceutical applications of this PA in skincare.
    Soft Matter 06/2013; 9(26):6033-6036. · 3.91 Impact Factor
  • Ian W Hamley, Ashkan Dehsorkhi, Valeria Castelletto
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    ABSTRACT: The self-assembly in water of a designed peptide amphiphile (PA) C16-ETTES containing two anionic residues, as well as its mixtures with C16-KTTKS containing two cationic residues has been investigated. Multiple spectroscopic, microscopic and scattering techniques are used to examine ordering extending from the β-sheet structures up to the fibrillar aggregate structure. The peptide amphiphiles both comprise a hexadecyl alkyl chain and a charged pentapeptide headgroup containing two glutamic acid residues. For C16-ETTES, the critical aggregation concentration was determined by thioflavin T fluorescence experiments. FTIR and CD spectroscopy were used to examine β-sheet formation. TEM revealed highly extended tape nanostructures with some striped regions corresponding to bilayer structures viewed "edge on". Small-angle X-ray scattering showed a main 5.3 nm bilayer spacing along with a 3 nm spacing. These spacings are assigned respectively to predominant hydrated bilayers and a fraction of dehydrated bilayers. Signs of co-operative self-assembly are observed in the mixtures including reduced bundling of peptide amphiphile aggregates (extended tape structures) and enhanced β-sheet formation.
    Langmuir 03/2013; · 4.38 Impact Factor
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    ABSTRACT: A thermal transition is observed in the peptide amphiphile C16-KTTKS (TFA salt) from nanotapes at 20 °C to micelles at higher temperature (the transition temperature depending on concentration). The formation of extended nanotapes by the acetate salt of this peptide amphiphile, which incorporates a pentapeptide from type I procollagen, has been studied previously [V. Castelletto et al., Chem. Commun., 2010, 46, 9185]. Here, proton NMR and SAXS provide evidence for the TFA salt spherical micelles at high temperature. The phase behavior, with a Krafft temperature separating insoluble aggregates (extended nanotapes) at low temperature from the high temperature micellar phase resembles that for conventional surfactants, however this has not previously been reported for peptide amphiphiles.
    Soft Matter 03/2013; 9(13):3558-3564. · 3.91 Impact Factor
  • Ian W Hamley, Ashkan Dehsorkhi, Valeria Castelletto
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    ABSTRACT: The surfactant-like peptide (Ala)(6)(Arg) is found to self-assemble into 3 nm-thick sheets in aqueous solution. Scanning transmission electron microscopy measurements of mass per unit area indicate a layer structure based on antiparallel dimers. At higher concentration the sheets wrap into unprecedented ultrathin helical ribbon and nanotube architectures.
    Chemical Communications 01/2013; · 6.38 Impact Factor
  • Roanne R Jones, Valeria Castelletto, Che J Connon, Ian W Hamley
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    ABSTRACT: The collagen production of human dermal and corneal fibroblasts in contact with solutions of the peptide amphiphile (PA) C16-KTTKS is investigated, and related to its self-assembly into nanotapes structures. This PA is used in anti-wrinkle cosmeceutical applications (tradename MatrixylTM). We prove that C16-KTTKS stimulates collagen production in a concentration-dependent manner close to the critical aggregation concentration determined from pyrene fluorescence spectroscopy. This suggests that self-assembly and the stimulation of collagen production are inter-related.
    Molecular Pharmaceutics 01/2013; · 4.57 Impact Factor
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    ABSTRACT: Insulin-degrading enzyme (IDE) is a neutral Zn(2+) peptidase that degrades short peptides based on substrate conformation, size and charge. Some of these substrates, including amyloid β (Aβ) are capable of self-assembling into cytotoxic oligomers. Based on IDE recognition mechanism and our previous report of the formation of a stable complex between IDE and intact Aβ in vitro and in vivo, we analyzed the possibility of a chaperone-like function of IDE. A proteolytically inactive recombinant IDE with Glu111 replaced by Gln (IDEQ) was used. IDEQ blocked the amyloidogenic pathway of Aβ yielding non-fibrillar structures as assessed by electron microscopy. Measurements of the kinetics of Aβ aggregation by light scattering showed that 1) IDEQ effect was promoted by ATP independent of its hydrolysis, 2) end products of Aβ-IDEQ co-incubation were incapable of "seeding" the assembly of monomeric Aβ and 3) IDEQ was ineffective in reversing Aβ aggregation. Moreover, Aβ aggregates formed in the presence of IDEQ were non-neurotoxic. IDEQ had no conformational effects upon insulin (a non-amyloidogenic protein under physiological conditions) and did not disturb insulin receptor activation in cultured cells. Our results suggest that IDE has a chaperone-like activity upon amyloid-forming peptides. It remains to be explored whether other highly conserved metallopeptidases have a dual protease-chaperone function to prevent the formation of toxic peptide oligomers from bacteria to mammals.
    PLoS ONE 01/2013; 8(4):e59113. · 3.73 Impact Factor
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    ABSTRACT: The development of versatile bioactive surfaces able to emulate in vivo conditions is of enormous importance to the future of cell and tissue therapy. Tuning cell behaviour on two-dimensional surfaces so that the cells perform as if they were in a natural three-dimensional tissue represents a significant challenge, but one that must be met if the early promise of cell and tissue therapy is to be fully realised. Due to the inherent complexities involved in the manufacture of biomimetic three-dimensional substrates, the scaling up of engineered tissue-based therapies may be simpler if based upon proven two-dimensional culture systems. In this work, we developed new coating materials composed of the self-assembling peptide amphiphiles (PAs) C 16 G 3 RGD (RGD) and C 16 G 3 RGDS (RGDS) shown to control cell adhesion and tissue architecture while avoiding the use of serum. When mixed with the C 16 ETTES diluent PA at 13 : 87 (mol mol À1) ratio at 1.25 Â 10 À3 M, the bioactive PAs were shown to support optimal adhesion, maximal proliferation, and prolonged viability of human corneal stromal fibroblasts (hCSFs), while improving the cell phenotype. These PAs also provided stable adhesive coatings on highly-hydrophobic surfaces composed of striated polytetrafluoroethylene (PTFE), significantly enhancing proliferation of aligned cells and increasing the complexity of the produced tissue. The thickness and structure of this highly-organised tissue were similar to those observed in vivo, comprising aligned newly-deposited extracellular matrix. As such, the developed coatings can constitute a versatile biomaterial for applications in cell biology, tissue engineering, and regenerative medicine requiring serum-free conditions.
    Journal of Materials Chemistry 01/2013; · 5.97 Impact Factor
  • Soft Matter 01/2013; 9(19):4794-. · 3.91 Impact Factor
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    ABSTRACT: Here, we studied the self-assembly of two peptide amphiphiles, C16-Gly-Gly-Gly-Arg-Gly-Asp (PA 1: C16-GGG-RGD) and C16-Gly-Gly-Gly-Arg-Gly-Asp-Ser (PA 2: C16-GGG-RGDS). We showed that PA 1 and PA 2 self-assemble into nanotapes with an internal bilayer structure. C16 chains were highly interdigitated within the nanotape cores, while the peptide blocks formed water-exposed 13-sheets too. PA 1 nanotapes were characterized by one spacing distribution, corresponding to a more regular internal structure than that of PA 2 nanotapes, which presented two different spacing distributions. We showed that it is possible to obtain homogeneous nanotapes in water by co-assembling PA 1 or PA 2 with the negatively charged diluent C,16-Glu-Thr-Thr-Glu-Ser (PA 3: C16-ETTES). The homogeneous tapes formed by PA 1-PA 3 or PA 2-PA 3 mixtures presented a structure similar to that observed for the corresponding pure PA 1 or PA 2 nanotapes. The mixed nanotapes, which were able to form a stabilized matrix containing homogeneously distributed cell adhesive RGD groups, represent promising materials for designing new cell adhesion substrates.
    Faraday Discussions 01/2013; 166:381-97. · 3.82 Impact Factor
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    ABSTRACT: Here we explore the physico-chemical properties of a peptide amphiphile obtained by chemical conjugation of the collagen-stimulating peptide KTTKS with 10,12-pentacosadiynoic acid which photopolymerizes as a stable and extended polydiacetylene. We investigate the self-assembly of this new polymer and rationalize its peculiar behavior in terms of a thermal conformational transition. Surprisingly, this polymer shows a thermal transition associated with a non-cooperative increase in β-sheet content at high temperature.
    Chemical Communications 08/2012; 48(78):9774-6. · 6.38 Impact Factor
  • Valeria Castelletto, Ian W Hamley, Christopher Stain, Che Connon
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    ABSTRACT: We report on the formation of hydrogel monoliths formed by functionalized peptide Fmoc-RGD (Fmoc: fluorenylmethoxycarbonyl) containing the RGD cell adhesion tripeptide motif. The monolith is stable in water for nearly 40 days. The gel monoliths present a rigid porous structure consisting of a network of peptide fibers. The RGD-decorated peptide fibers have a β-sheet secondary structure. We prove that Fmoc-RGD monoliths can be used to release and encapsulate material, including model hydrophilic dyes and drug compounds. We provide the first insight into the correlation between the absorption and release kinetics of this new material and show that both processes take place over similar time scales.
    Langmuir 08/2012; 28(34):12575-80. · 4.38 Impact Factor
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    ABSTRACT: The influence of a non-ionic polymeric surfactant on the self-assembly of a peptide amphiphile (PA) that forms nanotapes is investigated using a combination of microscopic, scattering and spectroscopic techniques. Mixtures of Pluronic copolymer P123 with the PA C16-KTTKS in aqueous solution were studied at a fixed concentration of the PA at which it is known to self-assemble into extended nanotapes, but varying P123 concentration. We find that P123 can disrupt the formation of C16-KTTKS nanotapes, leading instead to cylindrical nanofibril structures. The spherical micelles formed by P123 at room temperature are disrupted in the presence of the PA. There is a loss of cloudiness in the solutions as the large nanotape aggregates formed by C16-KTTKS are broken up, by P123 solubilization. At least locally, β-sheet structure is retained, as confirmed by XRD and FTIR spectroscopy, even for solutions containing 20 wt% P123. This indicates, unexpectedly, that peptide secondary structure can be retained in solutions with high concentration of non-ionic surfactant. Self-assembly in this system exhibits slow kinetics towards equilibrium, the initial self-assembly being dependent on the order of mixing. Heating above the lipid chain melting temperature assists in disrupting trapped non-equilibrium states.
    Soft Matter 08/2012; 8(33):8608-8615. · 3.91 Impact Factor
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    ABSTRACT: Studying peptide amphiphiles (PAs), we investigate the influence of alkyl chain length on the aggregation behavior of the collagen-derived peptide KTTKS with applications ranging from antiwrinkle cosmetic creams to potential uses in regenerative medicine. We have studied synthetic peptides amphiphiles C(14)-KTTKS (myristoyl-Lys-Thr-Thr-Lys-Ser) and C(18)-KTTKS (stearoyl-Lys-Thr-Thr-Lys-Ser) to investigate in detail their physicochemical properties. It is presumed that the hydrophobic chain in these self-assembling peptide amphiphiles enhances peptide permeation across the skin compared to KTTKS alone. Subsequently C(n)-KTTKS should act as a prodrug and release the peptide by enzymatic cleavage. Our results should be useful in the further development of molecules with collagen-stimulating activity.
    Langmuir 07/2012; 28(33):12209-15. · 4.38 Impact Factor
  • V Castelletto, G Cheng, C Stain, C J Connon, I W Hamley
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    ABSTRACT: The self-assembly of the peptide amphiphile (PA) hexadecyl-(β-alanine-histidine) is examined in aqueous solution, along with its mixtures with multilamellar vesicles formed by DPPC (dipalmitoyl phosphatidylcholine). This PA, denoted C(16)-βAH, contains a dipeptide headgroup corresponding to the bioactive molecule L-carnosine. It is found to self-assemble into nanotapes based on stacked layers of molecules. Bilayers are found to coexist with monolayers in which the PA molecules pack with alternating up-down arrangement so that the headgroups decorate both surfaces. The bilayers become dehydrated as PA concentration increases and the number of layers in the stack decreases to produce ultrathin nanotapes comprised of 2-3 bilayers. Addition of the PA to DPPC multilamellar vesicles leads to a transition to well-defined unilamellar vesicles. The unique ability to modulate the stacking of this PA as a function of concentration, combined with its ability to induce a multilamellar to unilamellar thinning of DPPC vesicles, may be useful in biomaterials applications where the presentation of the peptide function at the surface of self-assembled nanostructures is crucial.
    Langmuir 07/2012; 28(31):11599-608. · 4.38 Impact Factor

Publication Stats

992 Citations
509.65 Total Impact Points

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Institutions

  • 2004–2014
    • University of Reading
      • Department of Chemistry
      Reading, England, United Kingdom
    • Universidade Federal do Ceará
      Ceará, Ceará, Brazil
  • 2013
    • University of Liverpool
      • Institute of Integrative Biology
      Liverpool, ENG, United Kingdom
  • 2008
    • National and Kapodistrian University of Athens
      • Division of Biochemistry
      Athens, Attiki, Greece
    • Diamond Light Source
      XPW, England, United Kingdom
  • 2005–2008
    • The University of York
      • Department of Chemistry
      York, England, United Kingdom
    • University of Santiago de Compostela
      • Departamento de Física de la Materia Condensada
      Santiago de Compostela, Galicia, Spain
  • 2001–2006
    • University of Leeds
      • School of Chemistry
      Leeds, ENG, United Kingdom