15 research outputs found

    Molecular assembly and mechanical properties of the extracellular matrix: A fibrous protein perspective

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    AbstractThe extracellular matrix is an integral and dynamic component of all tissues. Macromolecular compositions and structural architectures of the matrix are tissue-specific and typically are strongly influenced by the magnitude and direction of biomechanical forces experienced as part of normal tissue function. Fibrous extracellular networks of collagen and elastin provide the dominant response to tissue mechanical forces. These matrix proteins enable tissues to withstand high tensile and repetitive stresses without plastic deformation or rupture. Here we provide an overview of the hierarchical molecular and supramolecular assembly of collagens and elastic fibers, and review their capacity for mechanical behavior in response to force. This article is part of a Special Issue entitled: Fibrosis: Translation of basic research to human disease

    Polymorphisms in the human tropoelastin gene modify in vitro self-assembly and mechanical properties of elastin-like polypeptides.

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    Elastin is a major structural component of elastic fibres that provide properties of stretch and recoil to tissues such as arteries, lung and skin. Remarkably, after initial deposition of elastin there is normally no subsequent turnover of this protein over the course of a lifetime. Consequently, elastic fibres must be extremely durable, able to withstand, for example in the human thoracic aorta, billions of cycles of stretch and recoil without mechanical failure. Major defects in the elastin gene (ELN) are associated with a number of disorders including Supravalvular aortic stenosis (SVAS), Williams-Beuren syndrome (WBS) and autosomal dominant cutis laxa (ADCL). Given the low turnover of elastin and the requirement for the long term durability of elastic fibres, we examined the possibility for more subtle polymorphisms in the human elastin gene to impact the assembly and long-term durability of the elastic matrix. Surveys of genetic variation resources identified 118 mutations in human ELN, 17 being non-synonymous. Introduction of two of these variants, G422S and K463R, in elastin-like polypeptides as well as full-length tropoelastin, resulted in changes in both their assembly and mechanical properties. Most notably G422S, which occurs in up to 40% of European populations, was found to enhance some elastomeric properties. These studies reveal that even apparently minor polymorphisms in human ELN can impact the assembly and mechanical properties of the elastic matrix, effects that over the course of a lifetime could result in altered susceptibility to cardiovascular disease

    Mechanical properties of elastin-like peptides (ELPs) containing G to S substitutions.

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    <p>The four bar graphs indicate the means and standard errors for tensile mechanical properties of sheets of materials constructed with reference ELP, EP20–24–24, and ELPs containing the single G to S substitution. Materials constructed from ELPs containing the triple G to S substitution were too fragile to generate meaningful values. The number of replicates for each experiment (n) is indicated. ** indicates a significant difference between the two materials (ANOVA with Bonferoni correction, p<0.01).</p

    Single nucleotide polymorphisms causing non-synonymous changes in tropoelastin.

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    <p>Tropoelastin protein sequence corresponds to RefSeq, variant 1 (NM_000501). This variant does not include exons 22 or 26a (an extension of exon 26). Exons are boxed, with exon numbers above. The positions of mutations and substituted amino acids are indicated within the shaded boxes, minor allele is indicated second.</p

    Coacervation characteristics of select elastin-like peptides (ELPs).

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    <p>(A) Coacervation (temperature-induce phase separation) of reference ELP, EP20–24–24, and ELPs containing single and triple G to S substitutions. Time 0 corresponds to 20°C, and temperature was raised at a rate of 1°C/min. (B) Coacervation of reference ELP, EP20–24–24, and ELPs containing single and double K to R substitutions. Time 0 corresponds to 15°C, and temperature was raised at a rate of 1°C/min. Coacervation was followed by turbidity as measured by absorbance at 440 nm. Curves represent means for three replicate experiments. Note the curves for the K to R substitutions are shifted to the left indicating that coacervation is initiated at a lower temperature.</p

    Effect of introducing select amino acid substitutions on the secondary structure of elastin-like peptides (ELPs).

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    <p>(A) CD spectra comparing reference ELP, EP20–24–24, with ELPs containing single and triple G to S substitutions. (B) CD spectra comparing reference ELP, EP20–24–24, with ELPs containing single and double K to R substitutions. Compared to the reference polypeptide, the introduction of the substitutions does not appear to result in any major changes in conformation of these ELPs.</p
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