仿生糖胺聚糖底物的硫酸化控制生长因子的结合以及随后的神经和神经胶质细胞生长。,Biomaterials Science

当前位置： X-MOL 学术 › Biomater. Sci. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

仿生糖胺聚糖底物的硫酸化控制生长因子的结合以及随后的神经和神经胶质细胞生长。
Biomaterials Science ( IF 5.8 ) Pub Date : 2019-08-13 , DOI: 10.1039/c9bm00964g
Waddah Malaeb ₁ , Hisham F Bahmad ₂ , Wassim Abou-Kheir ₂ , Rami Mhanna ₁

Affiliation

硫酸糖胺聚糖（GAG）是主要通过其与生长因子的相互作用而参与众多信号通路的关键结构和功能性细胞外基质（ECM）分子。藻酸盐硫酸盐模拟硫酸化的GAG，并结合生长因子，例如碱性成纤维细胞生长因子（FGF-2）。在这里，通过使用生物素-链霉亲和素结合将具有不同硫酸化度（DS，从0到2.7）的生物素化藻酸盐硫酸盐固定在金和聚苯乙烯基质上，从而设计了天然仿生基质。使用带有耗散监测（QCM-D）和免疫组织化学的石英晶体微量天平，评估了膜的形成以及DS和生物素化方法对FGF-2结合的影响。底物硫酸化和FGF-2负载对A172（多形胶质母细胞瘤）生长的作用，SH-SY5Y（人类神经母细胞瘤）和PC-12（大鼠嗜铬细胞瘤）细胞系在体外通过增殖和神经突生长评估来评估。藻酸盐的DS的增加导致FGF-2结合增加，这通过用QCM-D测量并通过免疫染色证实的更高的频率和耗散变化来证明。所有硫酸盐化藻酸盐底物都比对照组更好地支持神经/神经胶质细胞系的附着和生长，在最高DS下观察到细胞增殖的增加最高（对于所有细胞系，p <0.05）。此外，具有最高DS的FGF-2负载底物诱导了神经突阳性PC-12细胞和平均神经突长度的最大增加。研发的仿生涂料可用于功能化生物传感应用的基材（例如，

"点击查看英文标题和摘要"

The sulfation of biomimetic glycosaminoglycan substrates controls binding of growth factors and subsequent neural and glial cell growth.

Sulfated glycosaminoglycans (GAGs) are key structural and functional extracellular matrix (ECM) molecules involved in numerous signaling pathways mainly through their interaction with growth factors. Alginate sulfate mimics sulfated GAGs and binds growth factors such as basic fibroblast growth factor (FGF-2). Here, natural biomimetic substrates were engineered by immobilizing biotinylated alginate sulfates with varying degrees of sulfation (DS, from 0 to 2.7) on gold and polystyrene substrates using biotin-streptavidin binding. The build-up of films and the effect of the DS and biotinylation method on FGF-2 binding were assessed using quartz crystal microbalance with dissipation monitoring (QCM-D) and immunohistochemistry. The role of substrate sulfation and FGF-2 loading on the growth of A172 (human glioblastoma multiforme), SH-SY5Y (human neuroblastoma), and PC-12 (rat pheochromocytoma) cell lines was evaluated in vitro using proliferation and neurite outgrowth assessment. An increase in the DS of alginates resulted in augmented FGF-2 binding as evidenced by higher frequency and dissipation shifts measured with QCM-D and confirmed with immunostaining. All sulfated alginate substrates supported the attachment and growth of neural/glial cell lines better than controls with the highest increase in cell proliferation observed for the highest DS (p < 0.05 for all the cell lines). Moreover, FGF-2 loaded substrates with the highest DS induced the most significant increase in neurite-positive PC-12 cells and average neurite length. The developed biomimetic coatings can be used to functionalize substrates for biosensing applications (e.g. gold substrates) and to induce defined cellular responses via controlled growth factor delivery for basic and applied sciences.

更新日期：2019-08-06

点击分享查看原文

点击收藏

公开下载

阅读更多本刊新发论文本刊介绍/投稿指南