Self-Assembly and Collagen-Stimulating Activity of a Peptide Amphiphile Incorporating a Peptide Sequence from Lumican

Abstract

The self-assembly and bioactivity of a peptide amphiphile (PA) incorporating a 13-residue sequence derived from the last 13 amino acids of the C-terminus of lumican, C16-YEALRVANEVTLN, attached to a hexadecyl (C16) lipid chain have been examined. Lumican is a proteoglycan found in many types of tissue and is involved in collagen fibril organization. A critical aggregation concentration (cac) for the PA was determined through pyrene fluorescence measurements. The structure of the aggregates was imaged using electron microscopy, and twisted and curved nanotapes were observed. In situ small-angle X-ray scattering and fiber X-ray diffraction reveal that these tapes contain interdigitated bilayers of the PA molecules. FTIR and circular dichroism spectroscopy and fiber X-ray diffraction indicate that the lumican sequence in the PA adopts a β-sheet secondary structure. Cell assays using human dermal fibroblasts show that below the cac the PA displays good biocompatibility and also stimulates collagen production over a period of 3 weeks, exceeding a 2-fold enhancement for several concentrations. Thus, this PA has promise in future biological applications, in particular, in tissue engineering.

Lysine-based amino-functionalized lipids for gene transfection: 3D phase behaviour and transfection performance

“…Besides the distinct peaks, TH10, OH10 and OO10 show a shoulder at q E 1.6 Å À1 in the WAXS pattern, which can be associated with the Ca-Ca spacing (3.79 Å) comparable to b-sheet structures in proteins. 41 For TH10 and OH10, the peptide-mimicking character has been already found by grazing incidence X-ray diffraction (GIXD) at the air-water interface. 3 Furthermore, hydrogen bonds and the Ca-Ca spacing have been found in WAXS for the very similar lipid TH4.…”

The Effect of Lipidation on the Self-Assembly of the Gut-Derived Peptide Hormone PYY3–36

“…However from previous studies reported, using other fluorescent probes to compare to pyrene, the concentration dependence of I1 provides a reliable Page | 10 assay for cac values. 34,36 Results indicate that the cac values are lower for the peptide solutions at native pH compared to pH 2 and pH 8.…”

“…Pyrene is a fluorophore that is sensitive to the local hydrophobic environment, 33 and it has been used a number of times previously to determine the cac of peptides and peptide amphiphile molecules. [34][35] The cac of the peptides were calculated by measuring the fluorescence intensity of the I1 (λ = 373 nm) peak, corresponding to the first vibronic band of pyrene. The dependence of the intensity I1 (373 nm) with the peptide concentration is shown in Figure 2.…”

Transition of Nano-Architectures Through Self-Assembly of Lipidated β3-Tripeptide Foldamers

“…In most α-peptide amphiphiles the hydrophobic alkyl chain is typically introduced by coupling palmitic acid (C16) at the N-terminal amine of a short peptide (Stendahl et al, 2006;Missirlis et al, 2011;Hamley et al, 2013;Miravet et al, 2013;Moyer et al, 2013;Stupp and Palmer, 2014). Other reports have also shown that the control of α-peptide amphiphile assembly was not only due to the incorporation of alkyl chains, but also due to variation of sequence length (Marullo et al, 2013), or by incorporating specific residues within the peptide sequence (Löwik et al, 2005;Nieuwland et al, 2013;Hamley et al, 2015). Our results demonstrate that the lipid chain can be coupled at any residue without loss of self-assembly, however, the location of the acyl chain allows a transition of the nanoarchitecture from fibers to belts in peptides with identical elemental composition.…”