Sialylated Glycan Modulated Biomimetic Ion Nanochannels

Ion channels play key roles in regulating ion environment inside and outside the cell.Sialylated glycans at the terminal of voltage-gated ion channels(VGIC)are abundant and could directly control the switch of VGIC.At the same time,sialylated glycans on cell surface are also closely related to various physiological processes,such as virus infection,tumor growth and metastasis.Different sialylated glycan linkage isomers could lead to completely different physiological effects.However,the complex compositions of these linked isomers and the minor structural differences make them difficult to distinguish.This paper mainly focuses on the identification and differentiation of different sialylated glycans,we report a biomimetic ion nanochannel device that could be regulated by sialylated glycan precisely.The nanochannel device is composed by a chemically etched polyethylene terephthalate(PET)film featured with conical nanochannels and a polyethyleneimine-g-malcopyranoside(abbreviated to Mal-PEI).Maltose,core binding units in Mal-PEI,could form multiple hydrogen bonding interactions with sialylated glycan,which triggers globule-to-coil transition of the polymer chain and blocks transmembrane ion transport,resulting in a remarkable decrease in ionic current of the nanochannel device.By taking advantages of different ionic current changes,this device could precisely discriminate?2-3 and ?2-6 linked sialyllactose,as well as sialylated glycan and neutral saccharides.Further,laser scanning confocal microscopy,adsorption dynamics,atomic force microscopy,electrochemical impedance spectroscopy,isothermal titration microcalorimetry and nuclear magnetic resonance titration clearly prove the carbohydrate–carbohydrate interactions between the sialylated glycan and the materials,and provide evidences for the movement of the Mal-PEI polymer chain.This work constructs a sialylated glycan modulated nanochannel system with a selective and smart ion-gating behavior,exhibiting its unique advantages in sialylated glycan responsiveness and precise discrimination of its linkage isomers,which may promote many interesting applications in biosensors,bio-separation,single nanopore analysis,and microfluidic devices,particularly when the significance of sialylated glycan in life process is taken into consideration.Importantly,the nanochannel device could monitor the sialycation process of lactose catalyzed by ?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 a selective and smart ion-gating behavior,exhibiting its unique advantages in SG responsiveness and enzymatic activity monitoring...