A synthetic ion channel with anisotropic ligand response

Takahiro Muraoka,Ryo Sasaki,Kiyoto Kamagata,Mitsunori Ikeguchi,Kazushi Kinbara,Rinshi S Kasai,Tomoyuki Akutagawa,Norihisa Hoshino,Kazuhito V Tabata,Toru Ekimoto,Hiroyuki Noji,Kohei Sato,Kazuaki Ichimura,Daiki Noguchi

doi:10.1038/s41467-020-16770-z

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.

Highlights

Biological membranes play pivotal roles in the cellular activities
We report a totally synthetic multipass transmembrane channel that can be introduced in lipid bilayers unidirectionally, and shows anisotropic responses to ligands allowing reversible regulation of ion transportation through lipid bilayers
By mimicking a multipass transmembrane (MTM) structure seen in the proteinic ion channels constructed through folding of iterative hydrophilic and hydrophobic domains, we newly designed amphiphiles 1mer and 2mer (Fig. 1)

Summary

Introduction

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. Dynamic light scattering (DLS) measurements indicated that 1mer was dispersed in tetrahydrofuran (THF) and formed aggregates in water (Supplementary Fig. 4a). Microscopic observation by irradiation with 330–385 nm light to excite the BPO units, ring-shaped images corresponding to the GUVs were visualized, indicating the localization of 1mer in the DOPC liposomal membranes (Supplementary Fig. 15b).

Results

Conclusion