Direct discrimination of cell surface glycosylation signatures using a single pH-responsive boronic acid-functionalized polymer.

Direct discrimination of cell surface glycosylation signatures using a single pH-responsive boronic acid-functionalized polymer.
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DOI:
10.1039/d2sc02116a
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发表时间:
2022-11-09
期刊:
影响因子:
8.4
通讯作者:
--
中科院分区:
化学1区
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--
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细胞表面聚糖在许多生物学过程中发挥重要作用,包括细胞-细胞相互作用、病原体感染和癌症转移。癌细胞表面具有与健康细胞不同的糖基化,使这些变化成为癌症的有用标志。然而,聚糖结构的多样性使得糖基化分析非常具有挑战性,聚糖“指纹”为评估细胞状态提供了重要工具。在这项工作中,我们利用硼酸(BA)部分与细胞表面聚糖的pH响应性差异结合来产生高含量的六通道基于BA的传感器阵列,该阵列使用单一聚合物来区分哺乳动物细胞类型。该传感平台提供了癌细胞的有效区分,并且容易区分中国仓鼠卵巢(CHO)糖突变体,提供了区分是聚糖驱动的证据。BA-官能化的聚合物传感器阵列易于扩展,为细胞表面糖基化相关疾病提供了新的诊断和治疗策略。开发了一种高含量的多通道传感器阵列,以有效地区分细胞状态。硼酸与聚糖的结合是pH响应性的,因此利用三种pH提供了来自单一聚合物的灵敏多维阵列。
Cell surface glycans serve fundamental roles in many biological processes, including cell–cell interaction, pathogen infection, and cancer metastasis. Cancer cell surface have alternative glycosylation to healthy cells, making these changes useful hallmarks of cancer. However, the diversity of glycan structures makes glycosylation profiling very challenging, with glycan ‘fingerprints’ providing an important tool for assessing cell state. In this work, we utilized the pH-responsive differential binding of boronic acid (BA) moieties with cell surface glycans to generate a high-content six-channel BA-based sensor array that uses a single polymer to distinguish mammalian cell types. This sensing platform provided efficient discrimination of cancer cells and readily discriminated between Chinese hamster ovary (CHO) glycomutants, providing evidence that discrimination is glycan-driven. The BA-functionalized polymer sensor array is readily scalable, providing access to new diagnostic and therapeutic strategies for cell surface glycosylation-associated diseases. A high-content multichannel sensor array was developed to efficiently discriminate cell states. The binding of boronic acid with glycans is pH-responsive, hence utilizing three pH provides a sensitive multidimensional array from a single polymer.
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