Raspanti Mario, Viola Manuela, Forlino Antonella, Tenni Ruggero, Gruppi Cristian, Tira Maria Enrica
Department of Human Anatomy, Insubria University, Varese, Italy.
J Struct Biol. 2008 Oct;164(1):134-9. doi: 10.1016/j.jsb.2008.07.001. Epub 2008 Jul 10.
Current wisdom on intermolecular interactions in the extracellular matrix assumes that small proteoglycans bind collagen fibrils on highly specific sites via their protein core, while their carbohydrate chains interact with each other in the interfibrillar space. The present study used high-resolution scanning electron microscopy to analyse the interaction of two small leucine-rich proteoglycans and several glycosaminoglycan chains with type I collagen fibrils obtained in vitro in a controlled, cell-free environment. Our results show that most ligands directly influence the collagen fibril size and shape, and their aggregation into thicker bundles. All chondroitin sulphate/dermatan sulphate glycosaminoglycans we tested, except chondroitin 4-sulphate, bound to the fibril surface in a highly specific way and, even in the absence of any protein core, formed regular, periodic interfibrillar links resembling those of the intact proteoglycan. Only intact decorin, however, was able to organize collagen fibrils into fibres compact enough to mimic in vitro the superfibrillar organization of natural tissues. Our data indicate that multiple interaction patterns may exist in vivo, may explain why decorin- or biglycan-knockout organisms show milder effects than can be expected, and may lead to the development of better, simpler engineered biomaterials.
目前关于细胞外基质中分子间相互作用的普遍观点认为，小分子蛋白聚糖通过其蛋白核心在高度特异性位点结合胶原纤维，而它们的碳水化合物链在纤维间空间相互作用。本研究使用高分辨率扫描电子显微镜分析了两种富含亮氨酸的小分子蛋白聚糖和几种糖胺聚糖链与在体外可控的无细胞环境中获得的I型胶原纤维的相互作用。我们的结果表明，大多数配体直接影响胶原纤维的大小和形状，以及它们聚集成更粗束状的过程。我们测试的所有硫酸软骨素/硫酸皮肤素糖胺聚糖，除了硫酸软骨素4-硫酸酯，都以高度特异性的方式结合到纤维表面，并且即使在没有任何蛋白核心的情况下，也形成了类似于完整蛋白聚糖的规则、周期性的纤维间连接。然而，只有完整的核心蛋白聚糖能够将胶原纤维组织成足够紧密的纤维，以在体外模拟天然组织的超纤维组织。我们的数据表明，体内可能存在多种相互作用模式，这可以解释为什么核心蛋白聚糖或双糖链蛋白聚糖基因敲除生物表现出比预期更温和的效应，并且可能导致更好、更简单的工程生物材料的开发。
