A highly selective ATP-responsive biomimetic nanochannel based on smart copolymer

ATP-sensitive potassium (K ATP ) channels couple intracellular metabolism to the electrical activity by regulating K + flux across the plasma membrane, thus playing an important role in both normal and pathophysiology. To understand the mechanism of ATP regulating biological ion channels, developing an ATP-responsive artificial nanochannel is an appealing but challenging topic because K ATP channel is a heteromultimer of two subunits (potassium channel subunit (Kir6.x) and sulfonylurea receptor (SUR)) and exhibit dynamic functions with adjustability and reversibility. Inspired by the structure of K ATP channels, we designed a smart copolymer modified nanochannel that may address the challenge. In the tricomponent poly( N -isopropylacrylamide) (PNIPAAm, PNI)-based copolymer system, phenylthiourea was used to bind the phosphate units of nucleotides and phenylboronic acid was introduced to combine the pentose ring of the nucleoside unit. Besides, a –COOH group with electron-withdrawing property was added into the phenylthiourea units, which may promote the hydrogen-bond-donating ability of thiourea . Specially, the smart copolymer not only provided static binding sites for recognition but also translated the recognition of ATP into their dynamic conformational transitions by changing the hydrogen-bonding environments surrounding PNIPAAm chains, thus achieving the gating function of nanochannel, which resembled the integration and coordination of Kir6.x and SUR units in active K ATP . The ATP-regulated ion channel exhibited excellent stability and reversibility. This study is the first example showing how to learn from nature to assemble the ATP-responsive artificial nanochannel and demonstrate the possible mechanism of ATP gating.