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

Abstract

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 Ca channels manipulated by InsPs, a smart poly[(N-isopropylacrylamide-co-4-(3-acryloylthioureido) benzoic acid)] (denoted as PNI-co-ATBA) 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 to 10 μmol L, as well as a clear discrimination among InsP, InsP, and InsP. This study indicates the great potential of biomolecule-responsive polymers in the fabrication of biomimetic ion nanochannels and other nanoscale biodevices.

Smart polymer-based calcium-ion self-regulated nanochannels by mimicking the biological Ca2+-induced Ca2+ release process

“…Then, electrolytes with different concentrations of CaCl 2 were separately added to the cell exposed to the PAA membrane. Figure 5b displays the CaCl 2 concentration dependence of the ionic current (at +0.2 V) change ratio [defined as (I − I 0 )/I 0 , where I 0 is the initial current] for the bare, PNIPAAm and PNI-co-CF 3 -PT 0.2 -co-DDDEEKC 0.2 -modified PAA membranes 45 . The detection range for Ca 2+ extended from 1 × 10 −4 mol L −1 to an ultratrace level of 1 × 10 −11 mol L −1 , which fully covered the intracellular and extracellular Ca 2+ / 1 × 10 −8 to 1 × 10 −3 mol L −157,58 and makes it possible to further utilize this artificial nanochannel for medical treatment.…”

“…A piece of PAA membrane (bare or modified) was mounted between a two-compartment electrochemical cell according to the literature 45 . Ag/AgCl electrodes were used to apply a transmembrane potential across the membrane.…”

Molecular Design of Solid‐State Nanopores: Fundamental Concepts and Applications

“…Inositol. Inspired by Ca 2+ ionic channels, a biomimetic inositol phosphate‐responsive nanopore device was built on AAO membranes . Inositol phosphate (InsP) is a signaling molecule and can be specifically recognized in the nanomolar range by a N ‐isopropylacrylamide‐ co ‐4‐(3‐acryloylthioureido) benzoic acid copolymer (PNI‐ co ‐ATBA) by hydrogen bond formation with the ATBA moieties.…”

Smart polymers driven by multiple and tunable hydrogen bonds for intact phosphoprotein enrichment

“…NIPAAm-co-ATBA 0.35 @SiO 2 was prepared through a typical surface-initiated atom transfer radical polymerization (SI-ATRP) according to the literature [34]. The rationality of the copolymer design has been validated in our previous work [27].…”

“…Furthermore, for the fabrication of novel phosphoprotein enrichment material, the developed responsive copolymer was grafted onto the porous silica gel (diameter 5 μm, inner pore size 350 Å) through SI-ATRP [34]. The copolymer-modified silica gel (denoted as NIPAAm-co-ATBA 0.35 @SiO 2 ) was characterized through scanning electron microscopy (SEM), nitrogen isothermal adsorption, thermal gravimetric analysis (TGA) and organic element analysis and zeta-potential analysis.…”