In situ polymerization of tropoelastin in the absence of chemical cross-linking

Mithieux, Suzanne M.; Tu, Yidong; Korkmaz, Emine; Braet, Filip; Weiss, Anthony S.

doi:10.1016/j.biomaterials.2008.10.018

Cited by 76 publications

(65 citation statements)

References 26 publications

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“…In this respect, it is interesting to note that coacervate droplets of full-length tropoelastin, which includes domain 30, are small and show a significant tendency to cluster (31,60). Moreover, in vitro imaging of hydrogel formation after coacervation of human tropoelastin has described network formation through clustering and partial coalescence of coacervate spheres (61).…”

Section: Proline Prevents the Aggregation Of Exposed Hydrophobicmentioning

confidence: 99%

Proline Periodicity Modulates the Self-assembly Properties of Elastin-like Polypeptides

Muiznieks

Keeley

2010

Journal of Biological Chemistry

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Elastin is a self-assembling protein of the extracellular matrix that provides tissues with elastic extensibility and recoil. The monomeric precursor, tropoelastin, is highly hydrophobic yet remains substantially disordered and flexible in solution, due in large part to a high combined threshold of proline and glycine residues within hydrophobic sequences. In fact, proline-poor elastin-like sequences are known to form amyloidlike fibrils, rich in ␤-structure, from solution. On this basis, it is clear that hydrophobic elastin sequences are in general optimized to avoid an amyloid fate. However, a small number of hydrophobic domains near the C terminus of tropoelastin are substantially depleted of proline residues. Here we investigated the specific contribution of proline number and spacing to the structure and self-assembly propensities of elastin-like polypeptides. Increasing the spacing between proline residues significantly decreased the ability of polypeptides to reversibly self-associate. Real-time imaging of the assembly process revealed the presence of smaller colloidal droplets that displayed enhanced propensity to cluster into dense networks. Structural characterization showed that these aggregates were enriched in ␤-structure but unable to bind thioflavin-T. These data strongly support a model where proline-poor regions of the elastin monomer provide a unique contribution to assembly and suggest a role for localized ␤-sheet in mediating self-assembly interactions.Elastin is the extracellular matrix protein responsible for the elasticity of vertebrate arterial vessels, connective tissues, lung, and skin. Elastin resilience is afforded by the formation of insoluble fibers, the first step of which involves the selfalignment of elastin monomers, tropoelastin, in a temperature-induced transition known as coacervation, through the association of hydrophobic domains (1, 2). Although highly (Ͼ75%) non-polar in character, tropoelastin remains predominantly monomeric and structurally disordered in solution (3-5) and critically, retains substantial backbone hydration and flexibility even when assembled (6) and cross-linked into mature, polymeric elastic arrays (7-13).Maintenance of structural heterogeneity and dynamics of the elastin backbone is achieved in large part by a high proportional composition of both proline (14%) and glycine (35%) residues within hydrophobic sequences (6, 14). These residues are commonly arranged into repeated motifs based on recurring sequence elements such as PGV and GVA. This includes a seven-fold tandem PGVGVA repeat in domain 24 of the native human elastin sequence (15). Contrary to enhancing coacervation or elastomeric properties, the multiple substitution of glycine residues for prolines within tandem repeat sequences (e.g. PGVGVA to GGVGVA) results in the formation of amyloid-like fibrils, rich in ␤-structure, from solution (6, 14). These structures are conformationally more restricted than native elastomeric sequences as a result of the tighter packing of residues into extended...

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Section: Proline Prevents the Aggregation Of Exposed Hydrophobicmentioning

confidence: 99%

Proline Periodicity Modulates the Self-assembly Properties of Elastin-like Polypeptides

Muiznieks

Keeley

2010

Journal of Biological Chemistry

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“…For example, MatriDerm, a collagen based scaffold with -elastin shows improved skin elasticity (Ryssel, Gazyakan et al 2008). Hydrogels formed exclusively from -elastin (Figure 3) favorably support attachment and proliferation of dermal fibroblasts in vitro (Annabi, Mithieux et al 2009;Annabi, Mithieux et al 2009 …”

Section: Hydrolyzed Elastin Materialsmentioning

confidence: 99%

“…Examples of synthetic elastin electrospun materials. Scanning electron micrographs of (A) human umbilical vein endothelial cells, (B) SMCs and (C) dermal fibroblasts cultured on synthetic elastin fibers These types of synthetic elastin hydrogels can be made by chemical cross-linking (Mithieux, Rasko et al 2004), enzyme treatment (Mithieux, Wise et al 2005) or raising the pH (Mithieux, Tu et al 2009) of rhTE solutions (Figure 4). The hydrogels demonstrate mechanical properties that are consistent with native elastin including low elastic moduli, support of attachment and proliferation of dermal fibroblasts (Mithieux, Rasko et al 2004;Rnjak, Li et al 2009;Annabi, Mithieux et al 2010).…”

Section: Recombinant Human Tropoelastinmentioning

confidence: 99%

“…Biomaterials 32(6): 1517-1525. Annabi, N., S. M. Mithieux, et al (2009). Synthesis of highly porous crosslinked elastin hydrogels and their interaction with fibroblasts in vitro.…”

Section: Referencesmentioning

confidence: 99%

“…Biomaterials 30(27): 4550-4557. Annabi, N., S. M. Mithieux, et al (2009). The fabrication of elastin-based hydrogels using high pressure CO(2).…”

Section: Referencesmentioning

confidence: 99%

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Elastin Based Constructs

Nivison‐Smith¹,

Weiss²

2011

Regenerative Medicine and Tissue Engineering - Cells and Biomaterials

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Highly Elastic Micropatterned Hydrogel for Engineering Functional Cardiac Tissue

Annabi

Tsang

Mithieux

et al. 2013

Adv Funct Materials

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216

205

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Heart failure is a major international health issue. Myocardial mass loss and lack of contractility are precursors to heart failure. Surgical demand for effective myocardial repair is tempered by a paucity of appropriate biological materials. These materials should conveniently replicate natural human tissue components, convey persistent elasticity, promote cell attachment, growth and conformability to direct cell orientation and functional performance. Here, microfabrication techniques are applied to recombinant human tropoelastin, the resilience-imparting protein found in all elastic human tissues, to generate photocrosslinked biological materials containing well-defined micropatterns. These highly elastic substrates are then used to engineer biomimetic cardiac tissue constructs. The micropatterned hydrogels, produced through photocrosslinking of methacrylated tropoelastin (MeTro), promote the attachment, spreading, alignment, function, and intercellular communication of cardiomyocytes by providing an elastic mechanical support that mimics their dynamic mechanical properties in vivo. The fabricated MeTro hydrogels also support the synchronous beating of cardiomyocytes in response to electrical field stimulation. These novel engineered micropatterned elastic gels are designed to be amenable to 3D modular assembly and establish a versatile, adaptable foundation for the modeling and regeneration of functional cardiac tissue with potential for application to other elastic tissues.

show abstract

In situ polymerization of tropoelastin in the absence of chemical cross-linking

Cited by 76 publications

References 26 publications

Proline Periodicity Modulates the Self-assembly Properties of Elastin-like Polypeptides

Proline Periodicity Modulates the Self-assembly Properties of Elastin-like Polypeptides

Elastin Based Constructs

Highly Elastic Micropatterned Hydrogel for Engineering Functional Cardiac Tissue

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