Role of fibulins in elastic fiber formation

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Elastic fibers provide elasticity to tissues of most higher vertebrates that undergo repeated stretch, such as large arteries, lung, elastic ligaments and skin. Elastic fiber formation in biological tissues is a highly organized mechanism, requiring numerous proteins and protein interactions. Among the important proteins in this process is a subset of the fibulin family of extracellular proteins. Fibulin-4 and -5, and to a lesser extent fibulin-3, have been shown to be critical for elastic fiber formation. The structural and functional basis for this role, however, is largely unknown. We will employ a combined biophysical, biochemical and cell biological approach using state of the art methodologies to determine structural features of these fibulins and their characteristics in calcium binding. We further aim to map interaction sites with known binding ligands and to identify novel unknown binding ligands, which may be important for elastic fiber formation. Functional contributions of interaction sites will be identified in cell culture approaches. It is expected that information gained from this project will not only enhance our basic understanding of elastic fiber formation, but will also help to generate new possibilities in obtaining synthetic advanced bio- and nanomaterials.