Our research group focuses on investigating the degradation of elastin fibers by various biologically relevant elastinolytic enzymes and on testing the peptides that are released during elastin degradation on their potential bioactivities.
Another focus lies on the structural characterization of native elastin from different tissues including skin, aorta, cartilage or elastic ligaments. Elastin is isolated from the respective tissue and subsequently characterized morphologically by scanning electron microscopy. Characterization on the molecular level is performed using mass spectrometric approaches.
Elastin and elastic fibers
Location and importance
Elastin is an essential protein of the extracellular matrix (ECM) of vertebrates. As the major component of elastic fibers, it provides elasticity and resilience to many connective tissues such as the aorta, lung, elastic cartilage, elastic ligaments and skin. The fibers are organized into distinct structures: concentric lamellae in blood vessels, honeycomb-like networks in elastic cartilage and ropelike fibers in lung, skin and ligaments. The properties of elastin and collagens complement one another in that they make the tissue tear-resistant and deformable.
SEM images of elastin fibers derived from skin, aorta and elastic cartilage, respectively.
Elastin shows a unique chemical composition, which is characterized by the presence of large amounts of the four amino acids glycine, alanine, valine and proline. Elastin is polymerized from its soluble precursor tropoelastin by extensive covalent cross-linking which is induced by the family of lysyl oxidases. These enzymes oxidatively deaminate most lysine residues in tropoelastin to form the corresponding α-aminoadipic-δ-semialdehydes. After formation of the reactive aldehydes that are also referred to as allysines, subsequent condensation reactions result in bi- and trifunctional cross-links as well as in the tetrafunctional cross-links desmosine and isodesmosine that are unique to elastin.
Unique cross-links in elastin: The tetrafunctional amino acid isomers desmosine and isodesmosine.
Properties and function
The cross-linking strengthens the biopolymer and makes it a flexible, insoluble and extremely durable structural protein with an exceptional half-life of about 74 years. Mature elastin is a vital component of the ECM as it forms the core material of the elastic fibers that are surrounded by a mantle of fibrillin-rich microfibrills. These fibers are very long-lasting assemblies that maintain their elastic function for the entire lifetime of the organism. Once produced mainly before birth and in the first years of life it is assumed to undergo no or little turnover under healthy conditions.
Studies have shown that elastin is not only a structure protein, which influences the biomechanical properties of the ECM, but also plays an important role during different physiological processes. Specific peptides that occur as a result of elastin and tropoelastin degradation may for instance influence angiogenesis and different cell activities such as cell adhesion, chemotaxis, migration, proliferation, protease activation and apoptosis. Such bioactive elastin peptides are denoted as matrikines (cleavage products of matrix proteins) or elastokines.
Alteration of elastin
Although elastin has a remarkably high half life and is highly resistant towards various influences, it can be damaged by proteases. In particular the aberrant expression of elastin-degrading enzymes such as matrix metalloproteinases or serine proteases can lead to damage and even a loss of function of elastic fibers.
SEM images of elastin fibers purified from human skin biopsies of 6-year-old and 90-year-old individuals, respectively.
The morphological damage of the elastic fiber network is a consequence of intrinsic aging.
Proteolytic damage together with the biological processes triggered by matrikines may support the development and progression of severe cardiovascular diseases such as aortic stenosis, arteriosclerosis, aortic aneurysm and lung emphysema and may play a role during skin aging and cancer progression. Overall, impairment of the elastic fiber assemblies have a strong impact upon mortality. Therefore, it is of great importance to investigate and understand elastin-degrading processes.