No abstract

Elastin provides structural integrity, biological cues and persistent elasticity to a range of important tissues including the vasculature and lungs. Its critical importance to normal physiology makes it a desirable component of biomaterials that seek to repair or replace these tissues. The recent availability of large quantities of the highly purified elastin monomer, tropoelastin, have allowed for a thorough characterization of the mechanical and biological mechanisms underpinning the benefits of mature elastin. While tropoelastin is a flexible molecule, a combination of optical and structural analyses has defined key regions of the molecule that directly contribute to the elastomeric properties and control the cell interactions of the protein. Insights into the structure and behavior of tropoelastin have translated into increasingly sophisticated elastin-like biomaterials, evolving from classically manufactured hydrogels and fibers to new forms, stabilized in the absence of incorporated cross-linkers. Tropoelastin is also compatible with synthetic and natural co-polymers, expanding the applications of its potential use beyond traditional elastin-rich tissues and facilitating finer control of biomaterial properties and the design of next-generation tailored bioactive materials.

The mechanical stability, elasticity, inherent bioactivity, and self-assembly properties of elastin make it a highly attractive candidate for the fabrication of versatile biomaterials. The ability to engineer specific peptide sequences derived from elastin allows for precise control of these physicochemical and organizational characteristics, and further broadens the diversity of elastin-based applications. Elastin and elastin-like peptides can also be modified or blended with other natural or synthetic moieties, including peptides, proteins, polysaccharides and polymers, to augment existing capabilities or confer additional architectural and biofunctional features to compositionally pure materials. Elastin and elastin-based composites have been subjected to diverse fabrication processes, including heating, electrospinning, wet spinning, solvent casting, freeze-drying, and cross-linking, for the manufacture of particles, fibers, gels, tubes, sheets and films. The resulting materials can be tailored to possess specific strength, elasticity, morphology, topography, porosity, wettability, surface charge and bioactivity. This extraordinary tunability of elastin-based constructs enables their use in a range of biomedical and tissue engineering applications such as targeted drug delivery, cell encapsulation, vascular repair, nerve regeneration, wound healing, and dermal, cartilage, bone and dental replacement.

Tropoelastin’s local and global structures dictate molecular dynamics and are essential for efficient assembly into elastin.

Protein folding poses unique challenges for large, disordered proteins due to the low resolution of structural data accessible in experiment and on the basis of short time scales and limited sampling attainable in computation. Such molecules are uniquely suited to accelerated-sampling molecular dynamics algorithms due to a flat-energy landscape. We apply these methods to report here the folded structure in water from a fully extended chain of tropoelastin, a 698-amino acid molecular precursor to elastic fibers that confer elasticity and recoil to tissues, finding good agreement with experimental data. We then study a series of artificial and disease-related mutations, yielding molecular mechanisms to explain structural differences and variation in hierarchical assembly observed in experiment. The present model builds a framework for studying assembly and disease and yields critical insight into molecular mechanisms behind these processes. These results suggest that proteins with disordered regions are suitable candidates for characterization by this approach.