Glioblastomas stem-like cells (GSCs) by invading the brain parenchyma escape resection and radiotherapy. GSC invasion is associated with altered N-glycosylation pattern of integrins and other transmembrane proteins resulting in changed mechanosensing but details are elusive. Because the tumour microenvironment has an increased stiffness we studied the interaction between matrix stiffness, N−glycosylation and GSC migration. To mimic the fibrillar microenvironments, we designed 3D−ex−polyacrylonitrile nanofibers scaffolds (NFS) with adjustable stiffnesses by loading multiwall carbon nanotubes (MWCNT). We found that migration of GSCs was maximum at 166 kPa. Migration rate was correlated with cell shape, expression of focal adhesion (FA), Epithelial to Mesenchymal Transition (EMT) proteins and (β1,6) branched N−glycan binding, galectin-3. Mutation of MGAT5 in GSC inhibited N−glycans (β1−6) branching, suppressed the stiffness dependence of FA and EMT protein expression as well as migration on 166kPa NFS; underpinning the role of multibranched N−glycans as a critical regulator of mechanotransduction by GSC.

中文翻译：

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胶质瘤干细胞侵袭性表型以最佳刚度受MGAT5依赖的机械传感驱动。

胶质母细胞瘤干样细胞（GSC）通过侵犯脑实质逃脱切除术和放射疗法。GSC入侵与整联蛋白和其他跨膜蛋白的N-糖基化模式改变相关，从而导致机械传感改变，但细节难以捉摸。因为肿瘤微环境的硬度增加，所以我们研究了基质硬度，N-糖基化和GSC迁移之间的相互作用。为了模拟原纤维微环境，我们通过加载多壁碳纳米管（MWCNT）设计了具有可调刚度的3D-ex-聚丙烯腈纳米纤维支架（NFS）。我们发现，GSC的迁移最大为166 kPa。迁移速率与细胞形状，粘着斑表达（FA），上皮向间质转化（EMT）蛋白和（β1,6）分支的N-聚糖结合，galectin-3相关。GSC中MGAT5的突变抑制了N-聚糖（β1-6）的分支，抑制了FA和EMT蛋白表达的刚性依赖性以及在166kPa NFS上的迁移；增强了多支化N-聚糖作为GSC机械转导的关键调节剂的作用。