A synthetic ion channel with anisotropic ligand response

Abstract

Biological membranes play pivotal roles in the cellular activities. Transmembrane proteins are the central molecules that conduct membrane-mediated biochemical functions such as signal transduction and substance transportation. Not only the molecular functions but also the supramolecular properties of the transmembrane proteins such as self-assembly, delocalization, orientation and signal response are essential for controlling cellular activities. Here we report anisotropic ligand responses of a synthetic multipass transmembrane ion channel. An unsymmetrical molecular structure allows for oriented insertion of the synthetic amphiphile to a bilayer by addition to a pre-formed membrane. Complexation with a ligand prompts ion transportation by forming a supramolecular channel, and removal of the ligand deactivates the transportation function. Biomimetic regulation of the synthetic channel by agonistic and antagonistic ligands is also demonstrated not only in an artificial membrane but also in a biological membrane of a living cell.

Imidazolinium‐based Multiblock Amphiphile as Transmembrane Anion Transporter

“…These results indicate that IMA is capable of ion transport only through the liquid phase membranes, thereby indicating IMA acts as a mobile carrier. Mobile carrier mechanism is a unique property of IMA , since our previously reported multiblock amphiphiles were all channel‐forming molecules [11–14] …”

“…Before the production runs, according to the default setups of the CHARMM‐GUI, an energy minimization and equilibration runs were executed sequentially. The setups of the equilibration runs were the same as those of our previous simulations [14] . The production runs were performed with the isothermal‐isobaric ensemble and the 2 fs timestep.…”

“…They consist of alternated structure of hydrophilic oligo(ethylene glycol) chains and hydrophobic aromatic moieties, which self‐assemble by π‐stack of aromatic moieties within the lipid bilayer membranes. The designs of these molecules were derived from multipass transmembrane proteins, which exhibit their functions by folding within the lipid bilayers [11–14] . Variable designs in hydrophobic moieties had enabled to develop diverse characteristics in ion transportation.…”

“…Membrane‐tension responsive ion channel formation was achieved by destabilization of aromatic stacking by introducing sterically hindered aromatic unit [12] . Reversible ligand‐gating ion transport was realized by incorporation of ligand‐binding phosphoric ester group to the boundary of hydrophilic and hydrophobic units [13,14] . Therefore, designing suitable hydrophobic unit is necessarily in developing diverse synthetic ion transport systems by multiblock amphiphile.…”

“…Herein, we applied this concept of molecular design to develop a new synthetic anion transporter. Non‐ionic, hydrophilic octa(ethylene glycol) (OEG) chains are located on the one end of hydrophobic diphenylacetylene units following our previously developed multiblock amphiphilic compounds [11–14] . In addition, imidazolinium was introduced to the center of the hydrophobic moiety, in between two diphenylacetylene units, as an anion recognition site (Scheme 1).…”