Department of Life Sciences, University of Modena and Reggio Emilia, Modena, Italy.
Department of Sciences, University of Basilicata, Potenza, Italy.
Sci Rep. 2018 Feb 15;8(1):3115. doi: 10.1038/s41598-018-21472-0.
Heparan sulfates (HSs) modulate tissue elasticity in physiopathological conditions by interacting with various matrix constituents as tropoelastin and elastin-derived peptides. HSs bind also to protein moieties accelerating amyloid formation and influencing cytotoxic properties of insoluble fibrils. Interestingly, amyloidogenic polypeptides, despite their supposed pathogenic role, have been recently explored as promising bio-nanomaterials due to their unique and interesting properties. Therefore, we investigated the interactions of HSs, obtained from different sources and exhibiting various degree of sulfation, with synthetic amyloidogenic elastin-like peptides (ELPs), also looking at the effects of these interactions on cell viability and cell behavior using in vitro cultured fibroblasts, as a prototype of mesenchymal cells known to modulate the soft connective tissue environment. Results demonstrate, for the first time, that HSs, with differences depending on their sulfation pattern and chain length, interact with ELPs accelerating aggregation kinetics and amyloid-like fibril formation as well as self-association. Furthermore, these fibrils do not negatively affect fibroblasts' cell growth and parameters of redox balance, and influence cellular adhesion properties. Data provide information for a better understanding of the interactions altering the elastic component in aging and in pathologic conditions and may pave the way for the development of composite matrix-based biomaterials.
硫酸乙酰肝素（HSs）通过与各种基质成分（如原弹性蛋白和弹性蛋白衍生肽）相互作用来调节生理病理条件下的组织弹性。HSs 还与蛋白部分结合，加速淀粉样蛋白形成并影响不溶性纤维的细胞毒性。有趣的是，尽管淀粉样多肽被认为具有致病作用，但由于其独特而有趣的特性，最近已被探索为有前途的生物纳米材料。因此，我们研究了 HSs 与合成的淀粉样弹性蛋白样肽（ELPs）之间的相互作用，HSs 来自不同的来源，具有不同程度的硫酸化，同时还观察了这些相互作用对细胞活力和细胞行为的影响，使用体外培养的成纤维细胞作为已知可调节软结缔组织环境的间充质细胞的原型。结果首次表明，HSs 根据其硫酸化模式和链长的不同，与 ELP 相互作用，加速聚集动力学和类似淀粉样纤维的形成以及自组装。此外，这些纤维不会对成纤维细胞的细胞生长和氧化还原平衡参数产生负面影响，并影响细胞黏附特性。这些数据为更好地理解在衰老和病理条件下改变弹性成分的相互作用提供了信息，并可能为开发基于复合基质的生物材料铺平道路。
