Developing an Inositol-Phosphate-Actuated Nanochannel System by Mimicking Biological Calcium Ion Channels

In eukaryotic cells, ion channels, which ubiquitously present as polypeptides or proteins, usually regulate the ion transport across biological membranes by conformational switching of the channel proteins in response to the binding of diverse signaling molecules (e.g., inositol phosphate, abbreviated to InsP). To mimic the gating behaviors of natural Ca²⁺ channels manipulated by InsPs, a smart poly[(N-isopropylacrylamide-co-4-(3-acryloylthioureido) benzoic acid)_0.2] (denoted as PNI-co-ATBA_0.2) was integrated onto a porous anodic alumina (PAA) membrane, building an InsP-actuated nanochannel system. Driven by the intensive hydrogen bonding complexation of ATBA monomer with InsP, the copolymer chains displayed a remarkable and reversible conformational transition from a contracted state to a swollen one, accompanied with significant changes in surface morphology, wettability, and viscoelasticity. Benefiting from these features, dynamic gating behaviors of the nanochannels located on the copolymer-modified PAA membrane could be precisely manipulated by InsPs, reflected as a satisfactory linear relationship between real-time variation in transmembrane ionic current and the InsP concentration over a wide range from 1 nmol L^-1 to 10 μmol L^-1, as well as a clear discrimination among InsP₂, InsP₃, and InsP₆. This study indicates the great potential of biomolecule-responsive polymers in the fabrication of biomimetic ion nanochannels and other nanoscale biodevices.