Role of fibulins in elastic fiber formation

弹性纤维为大多数经过反复拉伸的高等脊椎动物的组织提供弹性，如大动脉、肺、弹性韧带和皮肤。弹性纤维在生物组织中的形成是一个高度组织化的机制，需要大量的蛋白质和蛋白质的相互作用。在这个过程中重要的蛋白质是细胞外蛋白纤维蛋白家族的一个子集。纤维蛋白-4和-5，以及较小程度上的纤维蛋白-3，已被证明对弹性纤维的形成至关重要。然而，这种作用的结构和功能基础在很大程度上是未知的。我们将采用生物物理、生物化学和细胞生物学相结合的方法，使用最先进的方法来确定这些纤维蛋白的结构特征及其在钙结合中的特征。我们进一步的目标是绘制已知结合配体的相互作用位点，并鉴定新的未知结合配体，这可能对弹性纤维的形成很重要。相互作用位点的功能贡献将在细胞培养方法中确定。预计从该项目中获得的信息不仅将增强我们对弹性纤维形成的基本理解，而且将有助于为合成先进的生物和纳米材料提供新的可能性。

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.