Sialylated glycan-modulated biomimetic ion nanochannels driven by carbohydrate-carbohydrate interactions

Ion channels play key roles in regulating the ion environment inside and outside the cell. Sialylated glycans (SGs) at the terminus of voltage-gated ion channels (VGICs) are abundant and directly control the switch of VGICs, while SGs on the cell surface are also closely related to virus infection, tumor growth, and metastasis. Here, we report a biomimetic ion nanochannel device that can be precisely regulated by SG. The nanochannel device is composed of a chemically etched polyethylene terephthalate film featuring conical nanochannels and a polyethyleneimine-g-malcopyranoside (abbreviated to Mal-PEI). Maltose, core-binding units in Mal-PEI, forms multiple hydrogen-bonding interactions with SG, which triggers globule-to-coil transition of the polymer chain and blocks transmembrane ion transport, resulting in a remarkable decrease in the ionic current of the nanochannel. Based on the changes in the ionic current, this device can precisely discriminate alpha 2 3 and alpha 2 6 linked sialyllactose, as well as SGs and neutral saccharides. Importantly, the nanochannel device can monitor the sialylation process of lactose catalyzed by alpha 2,6-sialyltransferase in real time, showing its good potential in enzyme activity determination and in vitro enzyme identification. This work constructs an SG-modulated nanochannel with selective and smart ion-gating behavior, exhibiting unique advantages in SG responsiveness and enzymatic activity monitoring.