Selective detection of disease-associated changes in the glycocalyx is an emerging field in modern targeted therapies. Detecting minor glycan changes on the cell surface is a challenge exacerbated by the lack of correspondence between cellular DNA/RNA and glycan structures. We demonstrate that multivalent displays of lectins on DNA-barcoded phages—liquid lectin array (LiLA)—detect subtle differences in density of glycans on cells. LiLA constructs displaying 73 copies of diCBM40 (CBM) lectin per virion (φ-CBM₇₃) exhibit non-linear ON/OFF-like recognition of sialoglycans on the surface of normal and cancer cells. A high-valency φ-CBM₂₉₀ display, or soluble CBM protein, cannot amplify the subtle differences detected by φ-CBM₇₃. Similarly, multivalent displays of CBM and Siglec-7 detect differences in the glycocalyx between stem-like and non-stem populations in cancer. Multivalent display of lectins offer in situ detection of minor differences in glycocalyx in cells both in vitro and in vivo not feasible to currently available technologies.

中文翻译：

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液体凝集素阵列使用噬菌体上的多价 DNA 编码的凝集素检测组成糖萼差异


选择性检测糖萼中与疾病相关的变化是现代靶向治疗中的一个新兴领域。检测细胞表面的微小游离寡糖变化是一项挑战，由于细胞 DNA/RNA 和游离寡糖结构之间缺乏对应关系，这加剧了这一挑战。我们证明，DNA 条形码噬菌体（液体凝集素阵列 （LiLA））上凝集素的多价展示可检测细胞上聚糖密度的细微差异。每个病毒体 （φ-CBM₇₃） 显示 73 个拷贝的 diCBM40 （CBM） 凝集素的 LiLA 构建体在正常细胞和癌细胞表面表现出对唾液聚糖的非线性 ON/OFF 样识别。高价 φ-CBM₂₉₀ 显示或可溶性 CBM 蛋白无法放大 φ-CBM₇₃ 检测到的细微差异。同样，CBM 和 Siglec-7 的多价显示可检测癌症中茎样和非茎种群之间的糖萼差异。凝集素的多价展示可在体外和 体内对细胞 中糖萼的微小差异进行原位检测，这在目前可用的技术中是不可行的。