Molecular interactions between microfibrils and basement membranes

微原纤维在基底膜上的锚定是多细胞生物的普遍原理。本提案的具体主题集中在微原纤维-基底膜相互作用的分子机制上。我们提出以下几点建议：微纤维和基底膜蛋白之间的配体结合将用重组或组织来源的高纯度蛋白质进行检测。2. 为了检测“1”中未涵盖的蛋白质相互作用，我们将开发一种新的表面显示技术，并将其用于筛选微纤维蛋白和基底膜蛋白之间的配体结合相互作用。将开发具有人体透镜囊的模型系统。该系统允许我们测试基底膜内微原纤维的锚定和生长。微原纤维-基底膜界面的电镜表征。从这些项目中，我们期望对以下方面做出重要贡献：(i)了解基底膜与其环境的功能关系，（ii）组织工程（例如血管和皮肤等量物）的新策略，以及（iii）以微原纤维-基底膜界面为特征的疾病的治疗概念的发展。

Anchorage of microfibrils to basement membranes is a universal principle of multicellular organisms. The specific subjects of this proposal focus on molecular mechanisms of microfibril-basement membrane interactions. We propose the following approaches:1. Ligand binding between microfibrillar and basement membrane proteins will be examined with highly purified proteins from either recombinant or tissue sources. 2. To detect protein interactions not covered under "1", we will develop a new surface display technology and use it to screen for ligand binding interactions between microfibrillar and basement membrane proteins.3. A model system with human lens capsules will be developed. This system allows us to test anchorage and growth of microfibrils within basement membranes.4. Electron microscopic characterization of the microfibril-basement membrane interface.From these projects, we expect important contributions for (i) the understanding of functional relationships of basement membranes with their environment, (ii) new strategies in tissue engineering (e.g. blood vessels and skin equivalents), and (iii) the development of therapeutic concepts for diseases characterized by distrubed microfibrils-basement membrane interfaces.