Dataset Information

Noncovalent Modulation of the Inverse Temperature Transition and Self-Assembly of Elastin-b-Collagen-like Peptide Bioconjugates.

ABSTRACT: Stimuli-responsive nanostructures produced with peptide domains from the extracellular matrix offer great opportunities for imaging and drug delivery. Although the individual utility of elastin-like (poly)peptides and collagen-like peptides in such applications has been demonstrated, the synergistic advantages of combining these motifs in short peptide conjugates have surprisingly not been reported. Here, we introduce the conjugation of a thermoresponsive elastin-like peptide (ELP) with a triple-helix-forming collagen-like peptide (CLP) to yield ELP-CLP conjugates that show a remarkable reduction in the inverse transition temperature of the ELP domain upon formation of the CLP triple helix. The lower transition temperature of the conjugate enables the facile formation of well-defined vesicles at physiological temperature and the unexpected resolubilization of the vesicles at elevated temperatures upon unfolding of the CLP domain. Given the demonstrated ability of CLPs to modify collagens, our results not only provide a simple and versatile avenue for controlling the inverse transition behavior of ELPs, but also suggest future opportunities for these thermoresponsive nanostructures in biologically relevant environments.

SUBMITTER: Luo T

PROVIDER: S-EPMC4930074 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Noncovalent Modulation of the Inverse Temperature Transition and Self-Assembly of Elastin-b-Collagen-like Peptide Bioconjugates.

Luo Tianzhi T Kiick Kristi L KL

Journal of the American Chemical Society 20151203 49

Stimuli-responsive nanostructures produced with peptide domains from the extracellular matrix offer great opportunities for imaging and drug delivery. Although the individual utility of elastin-like (poly)peptides and collagen-like peptides in such applications has been demonstrated, the synergistic advantages of combining these motifs in short peptide conjugates have surprisingly not been reported. Here, we introduce the conjugation of a thermoresponsive elastin-like peptide (ELP) with a triple ...[more]

PMID: 26633746

Similar Datasets

Project description:BackgroundFibrosis plays an important role in both normal physiological and pathological phenomena as fibroblasts differentiate to myofibroblasts. The activation of fibroblasts is determined through interactions with the surrounding extracellular matrix (ECM). However, how this fibroblast-to-myofibroblast transition (FMT) is regulated and affected by elastin concentration in a three-dimensional (3D) microenvironment has not been investigated.MethodsWe developed an insoluble elastin-gradient 3D hydrogel system for long-lasting cell culture and studied the molecular mechanisms of the FMT in embedded cells by nanoflow LC-MS/MS analysis along with validation through real-time PCR and immunofluorescence staining.ResultsBy optimizing pH and temperature, four 3D hydrogels containing fibroblasts were successfully fabricated having elastin concentrations of 0, 20, 50, and 80% in collagen. At the low elastin level (20%), fibroblast proliferation was significantly increased compared to others, and in particular, the FMT was clearly observed in this condition. Moreover, through mass spectrometry of the hydrogel environment, it was confirmed that differentiation proceeded in two stages. In the early stage, calcium-dependent proteins including calmodulin and S100A4 were highly associated. On the other hand, in the late stage after several passages of cells, distinct markers of myofibroblasts were presented such as morphological changes, increased production of ECM, and increased α-SMA expression. We also demonstrated that the low level of elastin concentration induced some cancer-associated fibroblast (CAF) markers, including PDGFR-β, and fibrosis-related disease markers, including THY-1.ConclusionUsing our developed 3D elastin-gradient hydrogel system, we evaluated the effect of different elastin concentrations on the FMT. The FMT was induced even at a low concentration of elastin with increasing CAF level via calcium signaling. With this system, we were able to analyze varying protein expressions in the overall FMT process over several cellular passages. Our results suggest that the elastin-gradient system employing nonlinear optics imaging provides a good platform to study activated fibroblasts interacting with the microenvironment, where the ECM plays a pivotal role.

Dataset Information

Noncovalent Modulation of the Inverse Temperature Transition and Self-Assembly of Elastin-b-Collagen-like Peptide Bioconjugates.

Publications

Noncovalent Modulation of the Inverse Temperature Transition and Self-Assembly of Elastin-b-Collagen-like Peptide Bioconjugates.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets